Antigen-binding protein constructs and uses thereof

ABSTRACT

Provided herein are antigen-binding protein constructs capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein said antigen binding is pH-dependent. Provided are also uses of said antigen-binding protein constructs.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Patent Application62/858,310 filed on Jun. 6, 2019 and U.S. Provisional Patent Application62/897,965 filed on Sep. 9, 2019. The contents of each of theseapplications are incorporated herein by reference in their entireties.

TECHNICAL FIELD

The present disclosure relates to the field of biotechnology, and morespecifically, to antigen-binding molecules.

BACKGROUND

Antibody-drug-conjugates have been designed to combat a variety ofdiseases. One particular advantage of this approach is the ability forantibody-drug conjugates to have cytostatic or cytotoxic effects.Despite years of development, improved antibody-drug conjugates aredesired.

SUMMARY

The present invention is based on the concept that antigen-bindingprotein constructs can be generated that display enhanced efficacy(e.g., one or more of an increase (e.g., a detectable increase) in toxinliberation in a target mammalian cell, an increase (e.g., a detectableincrease) in target mammalian cell killing, and an increase (e.g., adetectable increase) in endolysosomal delivery).

Provided herein are pharmaceutical compositions including an effectiveamount of an antigen-binding protein construct (ABPC) including a firstantigen-binding domain that is capable of specifically binding FOLR1 oran epitope of FOLR1 presented on the surface of a target mammalian cell,where (a) the dissociation rate of the first antigen-binding domain at apH of about 4.0 to about 6.5 is faster than the dissociation rate at apH of about 7.0 to about 8.0 or (b) the dissociation constant (KD) ofthe first antigen-binding domain at a pH of about 4.0 to about 6.5 isgreater than the KD at a pH of about 7.0 to about 8.0.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC is degraded in the target mammalian cell followinginternalization of the ABPC by the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a conjugated toxin, radioisotope, drug, orsmall molecule.

Also provided herein are pharmaceutical compositions including aneffective amount of an antigen-binding protein construct (ABPC)including: a first antigen-binding domain that is capable ofspecifically binding FOLR1 or an epitope of FOLR1 presented on thesurface of a target mammalian cell; and a conjugated toxin,radioisotope, drug, or small molecule, where (a) the dissociation rateof the first antigen-binding domain at a pH of about 4.0 to about 6.5 isfaster than the dissociation rate at a pH of about 7.0 to about 8.0 orthe dissociation constant (KD) of the first antigen-binding domain at apH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0to about 8.0 and (b) the composition provides for one or more of anincrease in toxin liberation in the target mammalian cell as compared toa composition including the same amount of a control ABPC, an increasein target mammalian cell killing as compared to a composition includingthe same amount of a control ABPC, and an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a heavy chain variable domain of mirvetuximab with one or moreamino acids substituted with a histidine, where the heavy chain variabledomain of mirvetuximab includes SEQ ID NO: 1, and/or a light chainvariable domain of mirvetuximab with one or more amino acids substitutedwith a histidine, where the light chain variable domain of mirvetuximabincludes SEQ ID NO: 2, (b) a heavy chain variable domain of STRO-002with one or more amino acids substituted with a histidine, where theheavy chain variable domain of STRO-002 includes SEQ ID NO: 105, and/ora light chain variable domain of STRO-002 with one or more amino acidssubstituted with a histidine, where the light chain variable domain ofSTRO-002 includes SEQ ID NO: 106, (c) a heavy chain variable domain offarletuzumab with one or more amino acids substituted with a histidine,where the heavy chain variable domain of farletuzumab includes SEQ IDNO: 184; and/or a light chain variable domain of farletuzumab with oneor more amino acids substituted with a histidine, where the light chainvariable domain of farletuzumab includes SEQ ID NO: 185.

In some embodiments of any of the pharmaceutical compositions describedherein, the first FOLR1-binding domain includes one of (a) through (c):(a) a heavy chain variable domain including a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 3-5, respectively, with collectively a total of one ormore amino acid positions in SEQ ID NOs: 3-5 substituted with ahistidine; and/or a light chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, with collectively atotal of one or more amino acid positions in SEQ ID NOs: 6-8 substitutedwith a histidine; (b) a heavy chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 107-109 respectively, with collectivelya total of one or more amino acid positions in SEQ ID NOs: 107-109substituted with a histidine; and/or a light chain variable domainincluding a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 110-112,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 110-112 substituted with a histidine; (c) aheavy chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 186-188, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 186-188 substituted with ahistidine; and a light chain variable domain including a CDR1, a CDR2,and a CDR3 of SEQ ID NOs: 189-191, respectively, with collectively atotal of one or more amino acid positions in SEQ ID NOs: 189-191substituted with a histidine.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a heavy chain variable domain that is at least 90% identical toSEQ ID NO: 1, where the heavy chain variable domain includes a histidineat one or more positions in SEQ ID NO: 1 selected from the groupconsisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60,97, 98, 99, 100, 102, 103, 105, and 107; and/or a light chain variabledomain that is at least 90% identical to SEQ ID NO: 2, where the lightchain variable domain includes a histidine at one or more positions inSEQ ID NO: 2 selected from the group consisting of: 28, 30, 31, 32, 34,35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 105, wherethe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 105 selected from the group consisting of: 29,33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111,112, and 113; and a light chain variable domain that is at least 90%identical to SEQ ID NO: 106: where the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 106 selectedfrom the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and96; (c) a heavy chain variable domain that is at least 90% identical toSEQ ID NO: 184, where the heavy chain variable domain includes ahistidine at one or more positions in SEQ ID NO: 184 selected from thegroup consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62,63, 103, and 105; and/or a light chain variable domain that is at least90% identical to SEQ ID NO: 185, where the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 185 selectedfrom the group consisting of 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94,96, 97, 98, 99, and 100.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a light chain variable domain of SEQ ID NO: 2, SEQ ID NO: 58,SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO:65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ IDNO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQID NO: 81, or SEQ ID NO: 83, and/or a heavy chain variable domain of SEQID NO: 1, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21,SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO:28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ IDNO: 35. SEQ ID NO: 36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53,SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO:89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ IDNO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97. SEQ ID NO: 98, SEQID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO:103, where the first antigen-binding domain does not comprise (i) alight chain variable domain of SEQ ID NO: 2 and heavy chain variabledomain of SEQ ID NO: 1; (ii) a light chain variable domain of SEQ ID NO:2 and heavy chain variable domain that is not one of SEQ ID NOs: 14, 17,19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103;(iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chainvariable domain that is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70,74, 76-81 and 83; and/or (b) a light chain variable domain of SEQ ID NO:106, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQID NO: 168, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO:180, SEQ ID NO: 181, or SEQ ID NO: 182, and/or a heavy chain variabledomain of SEQ ID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO:144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156; where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 106 and a heavy chain variable domain ofSEQ ID NO: 105; (ii) a light chain variable domain of SEQ ID NO: 106 anda heavy chain variable domain that is not one of SEQ ID NOs: 116,120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variabledomain of SEQ ID NO: 105 and a light chain variable domain that is notone of SEQ ID NOs: 161-164, 168, and 177-182; (c) a light chain variabledomain of SEQ ID NO: 185, SEQ ID NO: 233, SEQ ID NO: 237, SEQ ID NO:238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO:251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, orSEQ ID NO: 257, and/or a heavy chain variable domain of SEQ ID NO: 184,SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ IDNO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205,SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ IDNO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 185 and a heavy chain variable domain ofSEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 anda heavy chain variable domain that is not one of SEQ ID NOs: 192-196,198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) a heavychain variable domain of SEQ ID NO: 184 and a light chain variabledomain that is not one of SEQ ID NOs: 233, 237-244, 247, 249, 251, and253-257,

In some embodiments of any of the pharmaceutical compositions describedherein, the composition provides for an increase in toxin liberation inthe target mammalian cell as compared to a composition including thesame amount of a control ABPC; and/or an increase in target mammaliancell killing as compared to a composition including the same amount of acontrol ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the composition provides for an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the composition: results in a less of a reduction in the levelof FOLR1 presented on the surface of the target mammalian cell ascompared to a composition including the same amount of a control ABPC;or does not result in a detectable reduction in the level of FOLR1presented on the surface of the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the target mammalian cell is a cancer cell. In some embodimentsof any of the pharmaceutical compositions described herein, the ABPC iscytotoxic or cytostatic to the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC is cross-reactive with a non-human primate FOLR1 andhuman FOLR1 or cross-reactive with a non-human primate FOLR1, a humanFOLR1, and one or both of rat FOLR1 and a mouse FOLR1.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a single polypeptide. In some embodiments ofany of the pharmaceutical compositions described herein, theantigen-binding domain is selected from the group consisting of: a VHdomain, a VHH domain, a VNAR domain, and a scFv. In some embodiments ofany of the pharmaceutical compositions described herein, the ABPCincludes two or more polypeptides. In some embodiments of any of thepharmaceutical compositions described herein, the ABPC is an antibody.

In some embodiments of any of the pharmaceutical compositions describedherein, the half-life of the ABPC in vivo is decreased as compared tothe half-life of a control ABPC in vivo.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a second antigen-binding domain.

Also provided herein are an antigen-binding protein constructs (ABPCs)including a first antigen-binding domain that is capable of specificallybinding FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, where: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; or (b) thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0.

In some embodiments of any of the ABCPs described herein, the ABPC isdegraded in the target mammalian cell following internalization of theABPC by the target mammalian cell. In some embodiments of any of theABCPs described herein, the ABPC includes a conjugated toxin,radioisotope, drug, or small molecule.

Also provided herein are an antigen-binding protein constructs (ABPCs)including: a first antigen-binding domain that is capable ofspecifically binding FOLR1 or an epitope of FOLR1 presented on thesurface of a target mammalian cell; and a conjugated toxin,radioisotope, drug, or small molecule, where: (a) the dissociation rateof the first antigen-binding domain at a pH of about 4.0 to about 6.5 isfaster than the dissociation rate at a pH of about 7.0 to about 8.0; orthe dissociation constant (KD) of the first antigen-binding domain at apH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0to about 8.0; and (b) the composition provides for one or more of: anincrease in toxin liberation in the target mammalian cell as compared toa composition including the same amount of a control ABPC; an increasein target mammalian cell killing as compared to a composition includingthe same amount of a control ABPC; and an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the ABCPs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a heavychain variable domain of mirvetuximab with one or more amino acidssubstituted with a histidine, where the heavy chain variable domain ofmirvetuximab includes SEQ ID NO: 1; and/or a light chain variable domainof mirvetuximab with one or more amino acids substituted with ahistidine, where the light chain variable domain of mirvetuximabincludes SEQ ID NO: 2; (b) a heavy chain variable domain of STRO-002with one or more amino acids substituted with a histidine, where theheavy chain variable domain of STRO-002 includes SEQ ID NO: 105; and/ora light chain variable domain of STRO-002 with one or more amino acidssubstituted with a histidine, where the light chain variable domain ofSTRO-002 includes SEQ ID NO: 106; (c) a heavy chain variable domain offarletuzumab with one or more amino acids substituted with a histidine,where the heavy chain variable domain of farletuzumab includes SEQ IDNO: 184; and/or a light chain variable domain of farletuzumab with oneor more amino acids substituted with a histidine, where the light chainvariable domain of farletuzumab includes SEQ ID NO: 185.

In some embodiments of any of the ABCPs described herein, the firstFOLR1-binding domain includes one of (a) through (c): (a) a heavy chainvariable domain including a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 3-5 substituted with a histidine; and/or alight chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 6-8, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 6-8 substituted with a histidine;(b) a heavy chain variable domain including a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 107-109, respectively, with collectively a total of oneor more amino acid positions in SEQ ID NOs: 107-109 substituted with ahistidine; and/or a light chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 110-112, respectively, with collectivelya total of one or more amino acid positions in SEQ ID NOs: 110-112substituted with a histidine; (c) a heavy chain variable domainincluding a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 186-188,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 186-188 substituted with a histidine; and/or alight chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 189-191, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 189-191 substituted with ahistidine.

In some embodiments of any of the ABCPs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a heavychain variable domain that is at least 90% identical to SEQ ID NO: 1,where the heavy chain variable domain includes a histidine at one ormore positions in SEQ ID NO: 1 selected from the group consisting of:24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99; 100,102, 103, 105, and 107; and/or a light chain variable domain that is atleast 90% identical to SEQ ID NO: 2, where the light chain variabledomain includes a histidine at one or more positions in SEQ ID NO: 2selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55,59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 105, where the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 105 selected from the group consisting of: 29, 33, 34, 50, 51, 52,53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113; and/ora light chain variable domain that is at least 90% identical to SEQ IDNO: 106, where the light chain variable domain includes a histidine atone or more positions in SEQ ID NO: 106 selected from the groupconsisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; (c) a heavychain variable domain that is at least 90% identical to SEQ ID NO: 184,where the heavy chain variable domain includes a histidine at one ormore positions in SEQ ID NO: 184 selected from the group consisting of:26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105;and/or a light chain variable domain that is at least 90% identical toSEQ ID NO: 185, where the light chain variable domain includes ahistidine at one or more positions in SEQ ID NO: 185 selected from thegroup consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97,98, 99, and 100.

In some embodiments of any of the ABCPs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a lightchain variable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66,SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO:77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQID NO: 83, and/or a heavy chain variable domain of SEQ ID NO: 1, SEQ IDNO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30,SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO:36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ IDNO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 85, SEQID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88. SEQ ID NO: 89, SEQ ID NO: 90,SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO:95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103; where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 2 and heavy chain variable domain of SEQID NO: 1; (ii) a light chain variable domain of SEQ ID NO: 2 and heavychain variable domain that is not one of SEQ ID NOs: 14, 17, 19, 21-24,26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) a heavychain variable domain of SEQ ID NO: 1 and a light chain variable domainthat is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70, 74, 76-81 and83; and/or (b) a light chain variable domain of SEQ ID NO: 106, SEQ IDNO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 168,SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ IDNO: 181, or SEQ ID NO: 182, and/or a heavy chain variable domain of SEQID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO:122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156; where the firstantigen-binding domain does not comprise (i) a light chain variabledomain of SEQ ID NO: 106 and a heavy chain variable domain of SEQ ID NO:105; (ii) a light chain variable domain of SEQ ID NO: 106 and a heavychain variable domain that is not one of SEQ ID NOs: 116,120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variabledomain of SEQ ID NO: 105 and a light chain variable domain that is notone of SEQ ID NOs: 161-164, 168, and 177-182; (c) a light chain variabledomain of SEQ ID NO: 185, SEQ ID NO: 233, SEQ ID NO: 237, SEQ ID NO:238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO:251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, orSEQ ID NO: 257 and/or a heavy chain variable domain of SEQ ID NO: 184,SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ IDNO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205,SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ IDNO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 185 and a heavy chain variable domain ofSEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 anda heavy chain variable domain that is not one of SEQ ID NOs: 192-196,198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) a heavychain variable domain of SEQ ID NO: 184 and a light chain variabledomain that is not one of SEQ ID NOs: 233, 237-244, 247, 249, 251, and253-257.

In some embodiments of any of the ABCPs described herein, a compositionincluding the ABPC provides for an increase in toxin liberation in thetarget mammalian cell as compared to a composition including the sameamount of a control ABPC; and/or an increase in target mammalian cellkilling as compared to a composition including the same amount of acontrol ABPC.

In some embodiments of any of the ABCPs described herein, a compositionincluding the ABPC provides for an increase in endolysosomal delivery inthe target mammalian cell as compared to a composition including thesame amount of a control ABPC.

In some embodiments of any of the ABCPs described herein, a compositionincluding the ABPC results in a less of a reduction in the level ofFOLR1 presented on the surface of the target mammalian cell as comparedto a composition including the same amount of a control ABPC; or doesnot result in a detectable reduction in the level of FOLR1 presented onthe surface of the target mammalian cell.

In some embodiments of any of the ABCPs described herein, the targetmammalian cell is a cancer cell. In some embodiments of any of the ABCPsdescribed herein, the ABPC is cytotoxic or cytostatic to the targetmammalian cell.

In some embodiments of any of the ABCPs described herein, the ABPC iscross-reactive with a non-human primate FOLR1 and human FOLR1 orcross-reactive with a non-human primate FOLR1, a human FOLR1, and one orboth of rat FOLR1 and a mouse FOLR1.

In some embodiments of any of the ABCPs described herein, the ABPCincludes a single polypeptide.

In some embodiments of any of the ABCPs described herein, theantigen-binding domain is selected from the group consisting of: a VHdomain, a VHH domain, a VNAR domain, and a scFv. In some embodiments ofany of the ABCPs described herein, the ABPC includes two or morepolypeptides. In some embodiments of any of the ABCPs described herein,the ABPC is an antibody.

In some embodiments of any of the ABCPs described herein, the half-lifeof the ABPC in vivo is decreased as compared to the half-life of acontrol ABPC in vivo.

In some embodiments of any of the ABCPs described herein, the ABPCincludes a second antigen-binding domain.

Also provided herein are kits including at least one dose of thepharmaceutical composition of any one of the pharmaceutical compositionsdescribed herein or any one of the ABPCs described herein.

Also provided herein are methods of treating a cancer characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface, the method including, administering atherapeutically effective amount of the pharmaceutical composition ofany one of claims 1-20 or the ABPC of any one of claims 21-40 to asubject identified as having a cancer characterized by having thepopulation of cancer cells.

Also provided herein are methods of reducing the volume of a tumor in asubject, where the tumor is characterized by having a population ofcancer cells that have FOLR1 or an epitope of FOLR1 presented on theirsurface, the method including, administering a therapeutically effectiveamount of the pharmaceutical composition of any one of claims 1-20 orthe ABPC of any one of claims 21-40 to a subject identified as having acancer characterized by having the population of cancer cells.

Also provided herein are methods of inducing cell death in a cancer cellin a subject, where the cancer cell has FOLR1 or an epitope of FOLR1presented on its surface, where the method includes, administering atherapeutically effective amount of the pharmaceutical composition ofany one of claims 1-20 or the ABPC of any one of claims 21-40 to asubject identified as having a cancer characterized by having apopulation of the cancer cells.

Also provided herein are methods of decreasing the risk of developing ametastasis or decreasing the risk of developing an additional metastasisin a subject having a cancer, where the cancer is characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface the method including, administering atherapeutically effective amount of the pharmaceutical composition ofany one of claims 1-20 or the ABPC of any one of claims 21-40 to asubject identified as having a cancer characterized by having thepopulation of cancer cells.

Provided herein are pharmaceutical compositions including an effectiveamount of an antigen-binding protein construct (ABPC) including a firstantigen-binding domain that is capable of specifically binding FOLR1 oran epitope of FOLR1 presented on the surface of a target mammalian cell,where (a) the dissociation rate of the first antigen-binding domain at apH of about 4.0 to about 6.5 is faster than the dissociation rate at apH of about 7.0 to about 8.0 or (b) the dissociation constant (KD) ofthe first antigen-binding domain at a pH of about 4.0 to about 6.5 isgreater than the KD at a pH of about 7.0 to about 8.0.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC is degraded in the target mammalian cell followinginternalization of the ABPC by the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a conjugated toxin, radioisotope, drug, orsmall molecule.

Also provided herein are pharmaceutical compositions including aneffective amount of an antigen-binding protein construct (ABPC)including: a first antigen-binding domain that is capable ofspecifically binding FOLR1 or an epitope of FOLR1 presented on thesurface of a target mammalian cell; and a conjugated toxin,radioisotope, drug, or small molecule, where (a) the dissociation rateof the first antigen-binding domain at a pH of about 4.0 to about 6.5 isfaster than the dissociation rate at a pH of about 7.0 to about 8.0 orthe dissociation constant (KD) of the first antigen-binding domain at apH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0to about 8.0 and (b) the composition provides for one or more of anincrease in toxin liberation in the target mammalian cell as compared toa composition including the same amount of a control ABPC, an increasein target mammalian cell killing as compared to a composition includingthe same amount of a control ABPC, and an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a heavy chain variable domain of mirvetuximab with one or moreamino acids substituted with a histidine, where the heavy chain variabledomain of mirvetuximab includes SEQ ID NO: 1, and/or a light chainvariable domain of mirvetuximab with one or more amino acids substitutedwith a histidine, where the light chain variable domain of mirvetuximabincludes SEQ ID NO: 2, (b) a heavy chain variable domain of STRO-002with one or more amino acids substituted with a histidine, where theheavy chain variable domain of STRO-002 includes SEQ ID NO: 105, and/ora light chain variable domain of STRO-002 with one or more amino acidssubstituted with a histidine, where the light chain variable domain ofSTRO-002 includes SEQ ID NO: 106, (c) a heavy chain variable domain offarletuzumab with one or more amino acids substituted with a histidine,where the heavy chain variable domain of farletuzumab includes SEQ IDNO: 184; and/or a light chain variable domain of farletuzumab with oneor more amino acids substituted with a histidine, where the light chainvariable domain of farletuzumab includes SEQ ID NO: 185.

In some embodiments of any of the pharmaceutical compositions describedherein, the first FOLR1-binding domain includes one of (a) through (c):(a) a heavy chain variable domain including a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 3-5, respectively, with collectively a total of one ormore amino acid positions in SEQ ID NOs: 3-5 substituted with ahistidine; and/or a light chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, with collectively atotal of one or more amino acid positions in SEQ ID NOs: 6-8 substitutedwith a histidine; (b) a heavy chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 107-109 respectively, with collectivelya total of one or more amino acid positions in SEQ ID NOs: 107-109substituted with a histidine; and/or a light chain variable domainincluding a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 110-112,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 110-112 substituted with a histidine; (c) aheavy chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 186-188, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 186-188 substituted with ahistidine; and a light chain variable domain including a CDR1, a CDR2,and a CDR3 of SEQ ID NOs: 189-191, respectively, with collectively atotal of one or more amino acid positions in SEQ ID NOs: 189-191substituted with a histidine.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a heavy chain variable domain that is at least 90% identical toSEQ ID NO: 1, where the heavy chain variable domain includes a histidineat one or more positions in SEQ ID NO: 1 selected from the groupconsisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60,97, 98, 99, 100, 102, 103, 105, and 107; and/or a light chain variabledomain that is at least 90% identical to SEQ ID NO: 2, where the lightchain variable domain includes a histidine at one or more positions inSEQ ID NO: 2 selected from the group consisting of: 28, 30, 31, 32, 34,35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 105, wherethe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 105 selected from the group consisting of: 29,33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111,112, and 113; and a light chain variable domain that is at least 90%identical to SEQ ID NO: 106: where the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 106 selectedfrom the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and96; (c) a heavy chain variable domain that is at least 90% identical toSEQ ID NO: 184, where the heavy chain variable domain includes ahistidine at one or more positions in SEQ ID NO: 184 selected from thegroup consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62,63, 103, and 105; and/or a light chain variable domain that is at least90% identical to SEQ ID NO: 185, where the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 185 selectedfrom the group consisting of 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94,96, 97, 98, 99, and 100.

In some embodiments of any of the pharmaceutical compositions describedherein, the first antigen-binding domain includes one of (a) through(c): (a) a light chain variable domain of SEQ ID NO: 2, SEQ ID NO: 58,SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO:65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ IDNO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQID NO: 81, or SEQ ID NO: 83, and/or a heavy chain variable domain of SEQID NO: 1, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21,SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO:28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ IDNO: 35, SEQ ID NO: 36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53,SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO:89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ IDNO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO:103, where the first antigen-binding domain does not comprise (i) alight chain variable domain of SEQ ID NO: 2 and heavy chain variabledomain of SEQ ID NO: 1; (ii) a light chain variable domain of SEQ ID NO:2 and heavy chain variable domain that is not one of SEQ ID NOs: 14, 17,19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103;(iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chainvariable domain that is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70,74, 76-81 and 83; and/or (b) a light chain variable domain of SEQ ID NO:106; SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQID NO: 168; SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO:180, SEQ ID NO: 181; or SEQ ID NO: 182, and/or a heavy chain variabledomain of SEQ ID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO:144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156; where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 106 and a heavy chain variable domain ofSEQ ID NO: 105; (ii) a light chain variable domain of SEQ ID NO: 106 anda heavy chain variable domain that is not one of SEQ ID NOs: 105, 116,120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variabledomain of SEQ ID NO: 105 and a light chain variable domain that is notone of SEQ ID NOs: 161-164, 168, and 177-182; (c) a light chain variabledomain of SEQ ID NO: 185, SEQ ID NO: 233; SEQ ID NO: 237, SEQ ID NO:238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO:251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, orSEQ ID NO: 257, and/or a heavy chain variable domain of SEQ ID NO: 184,SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ IDNO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205,SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ IDNO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 185 and a heavy chain variable domain ofSEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 anda heavy chain variable domain that is not one of SEQ ID NOs: 184,192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii)a heavy chain variable domain of SEQ ID NO: 184 and a light chainvariable domain that is not one of SEQ ID NOs: 233, 237-244, 247, 249,251, and 253-257.

In some embodiments of any of the pharmaceutical compositions describedherein, the composition provides for an increase in toxin liberation inthe target mammalian cell as compared to a composition including thesame amount of a control ABPC; and/or an increase in target mammaliancell killing as compared to a composition including the same amount of acontrol ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the composition provides for an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the pharmaceutical compositions describedherein, the composition results in a less of a reduction in the level ofFOLR1 presented on the surface of the target mammalian cell as comparedto a composition including the same amount of a control ABPC or does notresult in a detectable reduction in the level of FOLR1 presented on thesurface of the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the target mammalian cell is a cancer cell. In some embodimentsof any of the pharmaceutical compositions described herein, the ABPC iscytotoxic or cytostatic to the target mammalian cell.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC is cross-reactive with a non-human primate FOLR1 andhuman FOLR1 or cross-reactive with a non-human primate FOLR1, a humanFOLR1, and one or both of rat FOLR1 and a mouse FOLR1.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a single polypeptide. In some embodiments ofany of the pharmaceutical compositions described herein, theantigen-binding domain is selected from the group consisting of: a VHdomain, a VHH domain, a VNAR domain, and a scFv. In some embodiments ofany of the pharmaceutical compositions described herein, the ABPCincludes two or more polypeptides. In some embodiments of any of thepharmaceutical compositions described herein, the ABPC is an antibody.

In some embodiments of any of the pharmaceutical compositions describedherein, the half-life of the ABPC in vivo is decreased as compared tothe half-life of a control ABPC in vivo.

In some embodiments of any of the pharmaceutical compositions describedherein, the ABPC includes a second antigen-binding domain.

Also provided herein are antigen-binding protein constructs (ABPCs)including a first antigen-binding domain that is capable of specificallybinding FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, where (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; or (b) thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0.

In some embodiments of any of the ABPCs described herein, the ABPC isdegraded in the target mammalian cell following internalization of theABPC by the target mammalian cell.

In some embodiments of any of the ABPCs described herein, the ABPCincludes a conjugated toxin, radioisotope, drug, or small molecule.

Also provided herein are an antigen-binding protein constructs (ABPCs)including a first antigen-binding domain that is capable of specificallybinding FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell; and a conjugated toxin, radioisotope, drug, orsmall molecule, where: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; or thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0; and (b) the composition provides for one or more of: anincrease in toxin liberation in the target mammalian cell as compared toa composition including the same amount of a control ABPC; an increasein target mammalian cell killing as compared to a composition includingthe same amount of a control ABPC; and an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositionincluding the same amount of a control ABPC.

In some embodiments of any of the ABPCs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a heavychain variable domain of mirvetuximab with one or more amino acidssubstituted with a histidine, where the heavy chain variable domain ofmirvetuximab includes SEQ ID NO: 1; and/or a light chain variable domainof mirvetuximab with one or more amino acids substituted with ahistidine, where the light chain variable domain of mirvetuximabincludes SEQ ID NO: 2; (b) a heavy chain variable domain of STRO-002with one or more amino acids substituted with a histidine, where theheavy chain variable domain of STRO-002 includes SEQ ID NO: 105; and/ora light chain variable domain of STRO-002 with one or more amino acidssubstituted with a histidine, where the light chain variable domain ofSTRO-002 includes SEQ ID NO: 106; (c) a heavy chain variable domain offarletuzumab with one or more amino acids substituted with a histidine,where the heavy chain variable domain of farletuzumab includes SEQ IDNO: 184; and/or a light chain variable domain of farletuzumab with oneor more amino acids substituted with a histidine, where the light chainvariable domain of farletuzumab includes SEQ ID NO: 185.

In some embodiments of any of the ABPCs described herein, the firstFOLR1-binding domain includes one of (a) through (c): (a) a heavy chainvariable domain including a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 3-5 substituted with a histidine; and/or alight chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 6-8, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 6-8 substituted with a histidine;(b) a heavy chain variable domain including a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 107-109, respectively, with collectively a total of oneor more amino acid positions in SEQ ID NOs: 107-109 substituted with ahistidine; and/or a light chain variable domain including a CDR1, aCDR2, and a CDR3 of SEQ ID NOs: 110-112, respectively, with collectivelya total of one or more amino acid positions in SEQ ID NOs: 110-112substituted with a histidine; (c) a heavy chain variable domainincluding a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 186-188,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 186-188 substituted with a histidine; and/or alight chain variable domain including a CDR1, a CDR2, and a CDR3 of SEQID NOs: 189-191, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 189-191 substituted with ahistidine.

In some embodiments of any of the ABPCs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a heavychain variable domain that is at least 90% identical to SEQ ID NO: 1,where the heavy chain variable domain includes a histidine at one ormore positions in SEQ ID NO: 1 selected from the group consisting of:24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100,102, 103, 105, and 107; and/or a light chain variable domain that is atleast 90% identical to SEQ ID NO: 2, where the light chain variabledomain includes a histidine at one or more positions in SEQ ID NO: 2selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55,59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 105, where the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 105 selected from the group consisting of: 29, 33, 34, 50, 51, 52,53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113; and/ora light chain variable domain that is at least 90% identical to SEQ IDNO: 106, where the light chain variable domain includes a histidine atone or more positions in SEQ ID NO: 106 selected from the groupconsisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; (c) a heavychain variable domain that is at least 90% identical to SEQ ID NO: 184,where the heavy chain variable domain includes a histidine at one ormore positions in SEQ ID NO: 184 selected from the group consisting of:26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105;and/or a light chain variable domain that is at least 90% identical toSEQ ID NO: 185, where the light chain variable domain includes ahistidine at one or more positions in SEQ ID NO: 185 selected from thegroup consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97,98, 99, and 100.

In some embodiments of any of the ABPCs described herein, the firstantigen-binding domain includes one of (a) through (c): (a) a lightchain variable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66,SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO:77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQID NO: 83, and/or a heavy chain variable domain of SEQ ID NO: 1, SEQ IDNO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30,SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO:36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ IDNO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 85, SEQID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90,SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO:95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ IDNO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103; where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 2 and heavy chain variable domain of SEQID NO: 1; (ii) a light chain variable domain of SEQ ID NO: 2 and heavychain variable domain that is not one of SEQ ID NOs: 14, 17, 19, 21-24,26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) a heavychain variable domain of SEQ ID NO: 1 and a light chain variable domainthat is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70, 74, 76-81 and83; and/or (b) a light chain variable domain of SEQ ID NO: 106, SEQ IDNO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 168,SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ IDNO: 181, or SEQ ID NO: 182, and/or a heavy chain variable domain of SEQID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO:122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 144, SEQ ID NO:145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156; where the firstantigen-binding domain does not comprise (i) a light chain variabledomain of SEQ ID NO: 106 and a heavy chain variable domain of SEQ ID NO:105; (ii) a light chain variable domain of SEQ ID NO: 106 and a heavychain variable domain that is not one of SEQ ID NOs: 116,120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variabledomain of SEQ ID NO: 105 and a light chain variable domain that is notone of SEQ ID NOs: 161-164, 168, and 177-182; (c) a light chain variabledomain of SEQ ID NO: 185, SEQ ID NO: 233, SEQ ID NO: 237, SEQ ID NO:238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO:251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, orSEQ ID NO: 257 and/or a heavy chain variable domain of SEQ ID NO: 184,SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ IDNO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205,SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ IDNO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, where thefirst antigen-binding domain does not comprise (i) a light chainvariable domain of SEQ ID NO: 185 and a heavy chain variable domain ofSEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 anda heavy chain variable domain that is not one of SEQ ID NOs: 192-196,198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) a heavychain variable domain of SEQ ID NO: 184 and a light chain variabledomain that is not one of SEQ ID NOs: 233, 237-244, 247, 249, 251, and253-257.

In some embodiments of any of the ABPCs described herein, a compositionincluding the ABPC provides for an increase in toxin liberation in thetarget mammalian cell as compared to a composition including the sameamount of a control ABPC; and/or an increase in target mammalian cellkilling as compared to a composition including the same amount of acontrol ABPC.

In some embodiments of any of the ABPCs described herein, a compositionincluding the ABPC provides for an increase in endolysosomal delivery inthe target mammalian cell as compared to a composition including thesame amount of a control ABPC.

In some embodiments of any of the ABPCs described herein, a compositionincluding the ABPC results in a less of a reduction in the level ofFOLR1 presented on the surface of the target mammalian cell as comparedto a composition including the same amount of a control ABPC; or doesnot result in a detectable reduction in the level of FOLR1 presented onthe surface of the target mammalian cell.

In some embodiments of any of the ABPCs described herein, the targetmammalian cell is a cancer cell. In some embodiments of any of the ABPCsdescribed herein, the ABPC is cytotoxic or cytostatic to the targetmammalian cell.

In some embodiments of any of the ABPCs described herein, the ABPC iscross-reactive with a non-human primate FOLR1 and human FOLR1; orcross-reactive with a non-human primate FOLR1, a human FOLR1, and one orboth of rat FOLR1 and a mouse FOLR1.

In some embodiments of any of the ABPCs described herein, the ABPCincludes a single polypeptide.

In some embodiments of any of the ABPCs described herein, theantigen-binding domain is selected from the group consisting of: a VHdomain, a VHH domain, a VNAR domain, and a scFv. In some embodiments ofany of the ABPCs described herein, the ABPC includes two or morepolypeptides. In some embodiments of any of the ABPCs described herein,the ABPC is an antibody.

In some embodiments of any of the ABPCs described herein, the half-lifeof the ABPC in vivo is decreased as compared to the half-life of acontrol ABPC in vivo.

In some embodiments of any of the ABPCs described herein, the ABPCincludes a second antigen-binding domain.

Also provided herein are kits including at least one dose of any of thepharmaceutical compositions described herein or any one of the ABPCsdescribed herein.

Also provided herein are methods of treating a cancer characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface, the method including administering atherapeutically effective amount of any one of the pharmaceuticalcompositions described herein or any one of the ABPCs described hereinto a subject identified as having a cancer characterized by having thepopulation of cancer cells.

Also provided herein are methods of reducing the volume of a tumor in asubject, where the tumor is characterized by having a population ofcancer cells that have FOLR1 or an epitope of FOLR1 presented on theirsurface, the method including administering a therapeutically effectiveamount of any of the pharmaceutical compositions described herein or anyone of the ABPCs described herein to a subject identified as having acancer characterized by having the population of cancer cells.

Also provided herein are methods of inducing cell death in a cancer cellin a subject, where the cancer cell has FOLR1 or an epitope of FOLR1presented on its surface, where the method includes administering atherapeutically effective amount of any one of the pharmaceuticalcompositions described herein or any one of the ABPCs described hereinto a subject identified as having a cancer characterized by having apopulation of the cancer cells.

Also provided herein are methods of decreasing the risk of developing ametastasis or decreasing the risk of developing an additional metastasisin a subject having a cancer, where the cancer is characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface the method including administering atherapeutically effective amount of any one of the pharmaceuticalcompositions described herein or any one of the ABPCs described hereinto a subject identified as having a cancer characterized by having thepopulation of cancer cells.

As used herein, the term “antigen-binding protein construct” is (i) asingle polypeptide that includes at least one antigen-binding domain or(ii) a complex of two or more polypeptides (e.g., the same or differentpolypeptides) that together form at least one antigen-binding domain.Non-limiting examples and aspects of antigen-binding protein constructsare described herein.

Additional examples and aspects of antigen-binding protein constructsare known in the art.

A “multi-specific antigen-binding protein construct” is anantigen-binding protein construct that includes two or more differentantigen-binding domains that collectively specifically bind two or moredifferent epitopes. The two or more different epitopes may be epitopeson the same antigen (e.g., a single polypeptide present on the surfaceof a cell) or on different antigens (e.g., different proteins present onthe surface of the same cell or present on the surface of differentcells). In some aspects, the antigen is present on the surface of thecell. In some aspects, a multi-specific antigen-binding proteinconstruct binds two different epitopes (i.e., a “bispecificantigen-binding protein construct”). In some aspects, a multi-specificantigen-binding protein construct binds three different epitopes (i.e.,a “trispecific antigen-binding protein construct”). In some aspects, amulti-specific antigen-binding protein construct binds four differentepitopes (i.e., a “quadspecific antigen-binding protein construct”). Insome aspects, a multi-specific antigen-binding protein construct bindsfive different epitopes (i.e., a “quintspecific antigen-binding proteinconstruct”). Each binding specificity may be present in any suitablevalency. Non-limiting examples of multi-specific antigen-binding proteinconstructs are described herein.

An “antigen-binding domain” is one or more protein domain(s) (e.g.,formed from amino acids from a single polypeptide or formed from aminoacids from two or more polypeptides (e.g., the same or differentpolypeptides) that is capable of specifically binding to one or moredifferent antigen(s). In some examples, an antigen-binding domain canbind to an antigen or epitope with specificity and affinity similar tothat of naturally-occurring antibodies. In some embodiments, theantigen-binding domain can be an antibody or a fragment thereof. In someembodiments, an antigen-binding domain can include an alternativescaffold. Non-limiting examples of antigen-binding domains are describedherein. Additional examples of antigen-binding domains are known in theart. In some examples, an antigen-binding domain can bind to a singleantigen.

The term “antibody” is used herein in its broadest sense and includescertain types of immunoglobulin molecules that include one or moreantigen-binding domains that specifically bind to an antigen or epitope.An antibody specifically includes, e.g., intact antibodies (e.g., intactimmunoglobulins, e.g., human IgG (e.g., human IgG1, human IgG2, humanIgG3, human IgG4)), antibody fragments, and multi-specific antibodies.One example of an antigen-binding domain is an antigen-binding domainformed by a VH-VL dimer. Additional examples of an antibody aredescribed herein. Additional examples of an antibody are known in theart.

The phrase “endosomal/lysosomal pathway” refers to a network ofendosomes (early endosomes, multi-vesicular bodies, late endosomes, andlysosomes) in the cytoplasm of a mammalian cell, wherein moleculesinternalized through cell-mediated internalization processes, e.g.,pinocytosis, micropinocytosis, receptor-mediated endocytosis, and/orphagocytosis, are sorted.

Once the endosomes in the endosomal/lysosomal pathway are purified orisolated, assays for a target protein (e.g., an antigen-binding proteinconstruct described herein) can be performed using methods known in theart (ELISA, Western blot, immunofluorescence, and immunoprecipitationfollowed by an assay for protein concentration), and can be used todetermine the concentration or relative level of the target protein inthe endosomes. Alternatively, endosomes in the endosomal/lysosomalpathway can be imaged using immunofluorescence microscopy using andetectably-labelled antibody (e.g., a fluorophore-labelled, adye-labelled, or a GFP-labelled antibody, e.g., CellLight™ EarlyEndosome-GFP) that specifically binds to a characteristic proteinpresent in the endosomes (e.g., EEA1 for early endosomes) and afluorophore-labelled antibody that specifically binds to the protein ofinterest (e.g., an antigen-binding protein construct), and the level ofthe target protein in the endosomes can be determined by quantitation ofthe overlap in the fluorescence emissions of the two differentantibodies.

The phrase “endolysosomal delivery” refers to rate of accumulation overtime or the total accumulation at a specific timepoint of anantigen-binding protein construct (e.g., any of the antigen-bindingprotein constructs described herein) in the endosomal/lysosomal pathwayin a mammalian cell (e.g., any of the exemplary target mammalian cellsdescribed herein).

An exemplary method to calculate the increase in endolysosomal deliveryof a pH engineered ABPC variant as compared to its correspondingstarting ABPC from cellular fluorescence data is to measure the ratio ofthe variant's mean fluorescence intensity minus the mean fluorescenceintensity of a non-binding IgG control, then all divided by thevariant's corresponding starting ABPC's mean fluorescence intensityminus the mean fluorescence intensity of the IgG control.

An exemplary assay for measuring endolysosomal delivery of any of theABPCs described herein include those which involve labeling of an ABPCwith a fluorescent dye, followed by incubation of the labeled ABPC withcells and measurement of cellular fluorescence as an indicator ofendolysosmal delivery of the ABPC (e.g., as described generally inWustner, Traffic 7(6):699-715, 2006). Alternatively, pH-sensitive dyeswhich preferentially fluoresce at acidic pH but not neutral pH can beused to label any of the ABPCs described herein, which can then beincubated with cells and the cellular fluorescence measured as anindicator of delivery of the ABPC into acidic endolysosomalcompartments.

The term “population” when used before a noun means two or more of thespecific noun. For example, the phrase “a population of cancer cells”means “two or more cancer cells.” Non-limiting examples of cancer cellsare described herein.

The phrase “cytostatic to a cell” refers to a direct or indirectdecrease in the proliferation (cell division) of the cell (e.g., acancer cell) in vivo or in vitro. When an agent is cytostatic to a cell,the agent can, e.g., directly or indirectly result in cell cycle arrestof the cell (e.g., a cancer cell). In some examples, an agent that iscytostatic to a cell can reduce the number of cells in a population ofthe cells that are in S phase (as compared to the number of cells in apopulation of the cells that are in S phase prior to contact with theagent). In some examples, an agent that is cytostatic to a cell canreduce the percentage of the cells in S phase by at least 20%, at least40%, at least 60%, or at least 80% (e.g., as compared to the percentageof cells in a population of the cells that are in S phase prior tocontact with the agent).

The phrase “cytotoxic to a cell” refers to the inducement, directly orindirectly, in the death (e.g., necrosis or apoptosis) of the cell(e.g., a mammalian cell, e.g., a cancer cell).

“Affinity” refers to the strength of the sum total of non-covalentinteractions between an antigen-binding site and its binding partner(e.g., an antigen or epitope). Unless indicated otherwise, as usedherein, “affinity” refers to intrinsic binding affinity, which reflectsa 1:1 interaction between members of an antigen-binding domain and anantigen or epitope. The affinity of a molecule X for its partner Y canbe represented by the dissociation equilibrium constant (KD). Affinitycan be measured by common methods known in the art, including thosedescribed herein. Affinity can be determined, for example, using surfaceplasmon resonance (SPR) technology (e.g., BIACORE®) or biolayerinterferometry (e.g., FORTEBIO®).

Additional methods for determining the affinity for an antigen-bindingdomain and its corresponding antigen or epitope are known in the art.

The term “epitope” means a portion of an antigen that is specificallybound by an antigen-binding domain through a set of physicalinteractions between: (i) all monomers (e.g. individual amino acidresidues, sugar side chains, and post-translationally modified aminoacid residues) on the portion of the antigen-binding domain thatspecifically binds the antigen and (ii) all monomers (e.g. individualamino acid residues, sugar side chains, post-translationally modifiedamino acid residues) on the portion of the antigen that is specificallybound by the antigen-binding domain. Epitopes can, e.g., consist ofsurface-accessible amino acid residues, sugar side chains,phosphorylated amino acid residues, methylated amino acid residues,and/or acetylated amino acid residues and may have specificthree-dimensional structural characteristics, as well as specific chargecharacteristics. Conformational and non-conformational epitopes aredistinguished in that binding to the former, but not the latter, may belost in the presence of denaturing solvents. In some embodiments, anepitope is defined by a linear amino acid sequence of at least about 3to 6 amino acids, or about 10 to 15 amino acids.

In some embodiments, an epitope refers to a portion of a full-lengthprotein or a portion thereof that is defined by a three-dimensionalstructure (e.g., protein folding). In some embodiments, an epitope isdefined by a discontinuous amino acid sequence that is brought togethervia protein folding. In some embodiments, an epitope is defined by adiscontinuous amino acid sequence that is brought together by quaternarystructure (e.g., a cleft formed by the interaction of two differentpolypeptide chains). The amino acid sequences between the residues thatdefine the epitope may not be critical to three-dimensional structure ofthe epitope. A conformational epitope may be determined and screenedusing assays that compare binding of antigen-binding protein constructto a denatured version of the antigen, such that a linear epitope isgenerated.

An epitope may include amino acid residues that are directly involved inthe binding, and other amino acid residues, which are not directlyinvolved in the binding.

Methods for identifying an epitope to which an antigen-binding domainspecifically binds are known in the art, e.g., structure-based analysis(e.g. X-ray crystallography, NMR, and/or electron microscopy) (e.g. onthe antigen and/or the antigen-antigen binding domain complex) and/ormutagenesis-based analysis (e.g. alanine scanning mutagenesis, glycinescanning mutagenesis, and homology scanning mutagenesis) wherein mutantsare measured in a binding assay with a binding partner, many of whichare known in the art.

The term “paratope” means a portion of an antigen-binding domain thatspecifically binds to an antigen through a set of physical interactionsbetween: (i) all monomers (e.g. individual amino acid residues, sugarside chains, posttranslationally modified amino acid residues) on theportion of the antigen-binding domain that specifically binds theantigen and (ii) all monomers (e.g. individual amino acid residues,sugar side chains, posttranslationally modified amino acid residues) onthe portion of the antigen that is specifically bound by theantigen-binding domain.

Paratopes can, e.g. consist of surface-accessible amino acid residuesand may have specific three-dimensional structural characteristics, aswell as specific charge characteristics. In some embodiments, a paratoperefers to a portion of a full-length antigen-binding domain or a portionthereof that is defined by a three-dimensional structure (e.g., proteinfolding). In some embodiments, a paratope is defined by a discontinuousamino acid sequence that is brought together via protein folding. Insome embodiments, an epitope is defined by a discontinuous amino acidsequence that is brought together by quaternary structure (e.g., a cleftformed by the

interaction of two different polypeptide chains). The amino acidsequences between the residues that define the paratope may not becritical to three-dimensional structure of the paratope. A paratope maycomprise amino acid residues that are directly involved in the binding,and other amino acid residues, which are not directly involved in thebinding.

Methods for identifying a paratope to which an antigen-binding domainspecifically binds are known in the art, e.g., structure-based analysis(e.g., X-ray crystallography, NMR, and/or electron microscopy) (e.g. onthe antigen-binding domain, and/or the antigen binding domain-antigencomplex), and/or mutagenesis-based analysis (e.g., alanine scanningmutagenesis, glycine scanning mutagenesis, and homology scanningmutagenesis) wherein mutants are measured in a binding assay with abinding partner, many of which are known in the art.

The phrase “present on the surface of a mammalian cell” means (1) anantigen that physically attached to or at least partially embedded inthe plasma membrane of a mammalian cell (e.g., a transmembrane protein,a peripheral membrane protein, a lipid-anchored protein (e.g., aGPI-anchor), an N-myristolyated protein, or a S-palmitoylated protein)or (2) an antigen that is stably bound to its cognate receptor, wherethe cognate receptor is physically attached to the plasma membrane of amammalian cell (e.g., a ligand bound to its cognate receptor, where thecognate receptor is physically attached to the plasma membrane).Non-limiting methods for determining the presence of antigen on thesurface of a mammalian cell include fluorescence-activated cell sorting(FACS), immunohistochemistry, cell-fractionation assays and Westernblotting.

The phrase “control ABPC” or “control antigen-binding protein construct”means (i) an ABPC that is capable of specifically binding to FOLR1 or anepitope of FOLR1 presented on the surface of a mammalian cell (e.g., atarget mammalian cell), where one or both of the following is true: (a)the dissociation rate of the first antigen-binding domain at a pH ofabout 4.0 to about 6.5 (e.g., any of the subranges of this rangedescribed herein) is no more than 3-fold (e.g., no more than 2.8-fold,no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, nomore than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, nomore than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, nomore than 1.2-fold, no more than 1.0-fold, no more than 0.8-fold, nomore than 0.6-fold, no more than 0.5-fold, no more than 0.4-fold, nomore than 0.3-fold no more than 0.2-fold, or no more than 0.1-fold)faster than the dissociation rate at a pH of about 7.0 to about 8.0(e.g., any of the subranges of this range described herein); or (b) thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 (e.g., any of the subranges of this rangedescribed herein) is no more than 3-fold (e.g., no more than 2.8-fold,no more than 2.6-fold, no more than 2.5-fold, no more than 2.4-fold, nomore than 2.2-fold, no more than 2.0-fold, no more than 1.8-fold, nomore than 1.6-fold, no more than 1.5-fold, no more than 1.4-fold, nomore than 1.2-fold, no more than 1.0-fold, no more than 0.8-fold, nomore than 0.6-fold, no more than 0.5-fold, no more than 0.4-fold, nomore than 0.3-fold no more than 0.2-fold, or no more than 0.1-fold)greater than the KD at a pH of about 7.0 to about 8.0 (e.g., any of thesubranges of this range described herein); and/or (ii) mirvetuximab;and/or (iii) STRO-002; and/or (iv) farletuzumab.

The term “extracellular space” means the liquid exterior to the plasmamembrane of a mammalian cell. When a mammalian cell is in vitro, theextracellular space can be a liquid culture medium. When a mammaliancell is in vivo, the extracellular space can be, e.g., plasma, serum,blood, interstitial fluid, or lymph.

The term “endolysosomal space” means the fluid encapsulated by thevesicles and organelles that make-up the endosomal/lysosomal pathway ina mammalian cell. The phrase “a reduced level” or “a decreased level”can be a reduction or decrease of at least a 1% (e.g., at least 2%, atleast 4%, at least 6%, at least 8%, at least 10%, at least 12%, at least14%, at least 16%, at least 18%, at least 20%, at least 22%, at least24%, at least 26%, at least 30%, at least 35%, at least 40%, at least45%, at least 50%, at least 55%, at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least95%, or at least 99%) reduction as compared to a reference level orvalue.

The term “cell killing potency” refers to the ability of an agent (e.g.,any of the ABPCs described herein) to induce, directly or indirectly,the apoptosis and/or necrosis of a mammalian cell (e.g., a cancer cell),measured as a rate over time or at a relevant timepoint. Methods fordetermining the cell killing potency of a cell are known in the art(e.g., trypan blue staining, microscopy, fluorescence-assisted cellsorting, and assays to detect markers of apoptosis (e.g., Annexin V)).In non-limiting examples, cell killing potency can be measured, e.g., bycell killing at a single concentration of an agent, by the IC50 of theagent (i.e. the concentration of the agent whereby half the maximal cellkilling potency is achieved), or by the ratio of an agent's dissociationconstant KD on mammalian cells divided by its IC50. In some non-limitingexamples, the IC50s and/or the KD ratios described herein are comparedto those of a control ABPC (as defined herein), and, optionally,demonstrate that the ABPCs described herein have a higher cell killingpotency as compared to the control ABPC.

The term “toxin liberation” refers to the ability of a mammalian cell(e.g., a non-cancerous mammalian cell or a cancer cell) to internalize(e.g., via pinocytosis and/or receptor-mediated endocytosis) any of theABPCs described herein (e.g., any of ABPCs or control ABPCs describedherein) that are conjugated to a toxin, and subsequently release thetoxin conjugated to the ABPC, measured as a rate over time or at aspecific timepoint. Toxin liberation can be assessed using a variety ofdifferent exemplary assays, e.g., ELISA, immunofluorescence, cellkilling assays, cell cycle arrest assays, DNA damage assays, massspectrometry, HPLC, and/or an isotope-labeled toxin.

The phrase “target cell” or “target mammalian cell” or “mammalian targetcell” means a mammalian cell that has at least one FOLR1 present on itssurface. In some examples, a mammalian target cell can be a cancer cell.In some embodiments of a target mammalian cell can have a total of about1 to about 10,000,000, about 1 to about 9,000,000, about 1 to about8,000,000, about 1 to about 7,000,000, about 1 to about 6,000,000, about1 to about 5,000,000, about 1 to about 4,000,000, about 1 to about3,000,000, about 1 to about 2,000,000, about 1 to about 1,000,000, about1 to about 800,000, about 1 to about 600,000, about 1 to about 400,000,about 1 to about 200,000, about 1 to about 100,000, about 1 to about80,000, about 1 to about 80,000, about 1 to about 75,000, about 1 toabout 70,000, about 1 to about 65,000, about 1 to about 60,000, about 1to about 55,000, about 1 to about 50,000, about 1 to about 45,000, about1 to about 40,000, about 1 to about 35,000, about 1 to about 30,000,about 1 to about 25,000, about 1 to about 20,000, about 1 to about15,000, about 1 to about 10,000, about 1 to about 7,500, about 1 toabout 5,000, about 1 to about 4,000, about 1 to about 3,000, about 1 toabout 2,000, about 1 to about 1,000, about 1 to about 500, about 1 toabout 100, about 1 to about 50, about 1 to about 10, about 10 to about10,000,000, about 10 to about 9,000,000, about 10 to about 8,000,000,about 10 to about 7,000,000, about 10 to about 6,000,000, about 10 toabout 5,000,000, about 10 to about 4,000,000, about 10 to about3,000,000, about 10 to about 2,000,000, about 10 to about 1,000,000,about 10 to about 800,000, about 10 to about 600,000, about 10 to about400,000, about 10 to about 200,000, about 10 to about 100,000, about 10to about 80,000, about 10 to about 80,000, about 10 to about 75,000,about 10 to about 70,000, about 10 to about 65,000, about 10 to about60,000, about 10 to about 55,000, about 10 to about 50,000, about 10 toabout 45,000, about 10 to about 40,000, about 10 to about 35,000, about10 to about 30,000, about 10 to about 25,000, about 10 to about 20,000,about 10 to about 15,000, about 10 to about 10,000, about 10 to about7,500, about 10 to about 5,000, about 10 to about 4,000, about 10 toabout 3,000, about 10 to about 2,000, about 10 to about 1,000, about 10to about 500, about 10 to about 100, about 10 to about 50, about 50 toabout 10,000,000, about 50 to about 9,000,000, about 50 to about8,000,000, about 50 to about 7,000,000, about 50 to about 6,000,000,about 50 to about 5,000,000, about 50 to about 4,000,000, about 50 toabout 3,000,000, about 50 to about 2,000,000, about 50 to about1,000,000, about 50 to about 800,000, about 50 to about 600,000, about50 to about 400,000, about 50 to about 200,000, about 50 to about100,000, about 50 to about 80,000, about 50 to about 80,000, about 50 toabout 75,000, about 50 to about 70,000, about 50 to about 65,000, about50 to about 60,000, about 50 to about 55,000, about 50 to about 50,000,about 50 to about 45,000, about 50 to about 40,000, about 50 to about35,000, about 50 to about 30,000, about 50 to about 25,000, about 50 toabout 20,000, about 50 to about 15,000, about 50 to about 10,000, about50 to about 7,500, about 50 to about 5,000, about 50 to about 4,000,about 50 to about 3,000, about 50 to about 2,000, about 50 to about1,000, about 50 to about 500, about 50 to about 100, about 100 to about10,000,000, about 100 to about 9,000,000, about 100 to about 8,000,000,about 100 to about 7,000,000, about 100 to about 6,000,000, about 100 toabout 5,000,000, about 100 to about 4,000,000, about 100 to about3,000,000, about 100 to about 2,000,000, about 100 to about 1,000,000,about 100 to about 800,000, about 100 to about 600,000, about 100 toabout 400,000, about 100 to about 200,000, about 100 to about 100,000,about 100 to about 80,000, about 100 to about 75,000, about 100 to about70,000, about 100 to about 65,000, about 100 to about 60,000, about 100to about 55,000, about 100 to about 50,000, about 100 to about 45,000,about 100 to about 40,000, about 100 to about 35,000, about 100 to about30,000, about 100 to about 25,000, about 100 to about 20,000, about 100to about 15,000, about 100 to about 10,000, about 100 to about 7,500,about 100 to about 5,000, about 100 to about 4,000, about 100 to about3,000, about 100 to about 2,000, about 100 to about 1,000, about 100 toabout 500, about 500 to about 10,000,000, about 500 to about 9,000,000,about 500 to about 8,000,000, about 500 to about 7,000,000, about 500 toabout 6,000,000, about 500 to about 5,000,000, about 500 to about4,000,000, about 500 to about 3,000,000, about 500 to about 2,000,000,about 500 to about 1,000,000, about 500 to about 800,000, about 500 toabout 600,000, about 500 to about 400,000, about 500 to about 200,000,about 500 to about 100,000, about 500 to about 80,000, about 500 toabout 75,000, about 500 to about 70,000, about 500 to about 65,000,about 500 to about 60,000, about 500 to about 55,000, about 500 to about50,000, about 500 to about 45,000, about 500 to about 40,000, about 500to about 35,000, about 500 to about 30,000, about 500 to about 25,000,about 500 to about 20,000, about 500 to about 15,000, about 500 to about10,000, about 500 to about 7,500, about 500 to about 5,000, about 500 toabout 4,000, about 500 to about 3,000, about 500 to about 2,000, about500 to about 1,000, about 1,000 to about 10,000,000, about 1,000 toabout 9,000,000, about 1,000 to about 8,000,000, about 1,000 to about7,000,000, about 1,000 to about 6,000,000, about 1,000 to about5,000,000, about 1,000 to about 4,000,000, about 1,000 to about3,000,000, about 1,000 to about 2,000,000, about 1,000 to about1,000,000, about 1,000 to about 800,000, about 1,000 to about 600,000,about 1,000 to about 400,000, about 1,000 to about 200,000, about 1,000to about 100,000, about 1,000 to about 80,000, about 1,000 to about75,000, about 1,000 to about 70,000, about 1,000 to about 65,000, about1,000 to about 60,000, about 1,000 to about 55,000, about 1,000 to about50,000, about 1,000 to about 45,000, about 1,000 to about 40,000, about1,000 to about 35,000, about 1,000 to about 30,000, about 1; 000 toabout 25,000, about 1,000 to about 20,000, about 1,000 to about 15,000,about 1; 000 to about 10,000, about 1,000 to about 7,500, about 1,000 toabout 5,000, about 1,000 to about 4,000, about 1,000 to about 3,000,about 1,000 to about 2,000, about 2,000 to about 10,000,000, about 2,000to about 9,000,000, about 2,000 to about 8,000,000, about 2,000 to about7,000,000, about 2,000 to about 6,000,000, about 2,000 to about5,000,000, about 2,000 to about 4,000,000, about 2,000 to about3,000,000, about 2,000 to about 2,000,000, about 2,000 to about1,000,000, about 2,000 to about 800,000, about 2,000 to about 600,000,about 2,000 to about 400,000, about 2,000 to about 200,000, about 2,000to about 100,000, about 2,000 to about 80,000, about 2,000 to about75,000, about 2,000 to about 70,000, about 2,000 to about 65,000, about2,000 to about 60,000, about 2,000 to about 55,000, about 2,000 to about50,000, about 2,000 to about 45,000, about 2,000 to about 40,000, about2,000 to about 35,000, about 2,000 to about 30,000, about 2,000 to about25,000, about 2,000 to about 20,000, about 2,000 to about 15,000, about2,000 to about 10,000, about 2,000 to about 7,500, about 2,000 to about5,000, about 2,000 to about 4,000, about 2,000 to about 3,000, about3,000 to about 10,000,000, about 3,000 to about 9,000,000, about 3,000to about 8,000,000, about 3,000 to about 7,000,000, about 3,000 to about6,000,000, about 3,000 to about 5,000,000, about 3,000 to about4,000,000, about 3,000 to about 3,000,000, about 3,000 to about2,000,000, about 3,000 to about 1,000,000, about 3,000 to about 800,000,about 3,000 to about 600,000, about 3,000 to about 400,000, about 3,000to about 200,000, about 3,000 to about 100,000, about 3,000 to about80,000, about 3,000 to about 75,000, about 3,000 to about 70,000, about3,000 to about 65,000, about 3,000 to about 60,000, about 3,000 to about55,000, about 3,000 to about 50,000, about 3,000 to about 45,000, about3,000 to about 40,000, about 3,000 to about 35,000, about 3,000 to about30,000, about 3,000 to about 25,000, about 3,000 to about 20,000, about3,000 to about 15,000, about 3,000 to about 10,000, about 3,000 to about7,500, about 3,000 to about 5,000, about 3.000 to about 4,000, about4,000 to about 10,000,000, about 4,000 to about 9,000,000, about 4,000to about 8,000,000, about 4,000 to about 7,000,000, about 4,000 to about6,000,000, about 4,000 to about 5,000,000, about 4,000 to about4,000,000, about 4,000 to about 3,000,000, about 4,000 to about2,000,000, about 4,000 to about 1,000,000, about 4,000 to about 800,000,about 4,000 to about 600,000, about 4,000 to about 400,000, about 4,000to about 200,000, about 4,000 to about 100,000, about 4,000 to about80,000, about 4,000 to about 75,000, about 4,000 to about 70,000, about4,000 to about 65,000, about 4,000 to about 60,000, about 4,000 to about55,000, about 4,000 to about 50,000, about 4,000 to about 45,000, about4,000 to about 40,000, about 4,000 to about 35,000, about 4,000 to about30,000, about 4,000 to about 25,000, about 4,000 to about 20,000, about4,000 to about 15,000, about 4,000 to about 10,000, about 4,000 to about7,500, about 4,000 to about 5,000, about 5,000 to about 10,000,000,about 5,000 to about 9,000,000, about 5.000 to about 8,000.000, about5,000 to about 7,000,000, about 5,000 to about 6,000,000, about 5,000 toabout 5,000,000, about 5,000 to about 4,000,000, about 5,000 to about3,000,000, about 5,000 to about 2,000,000, about 5,000 to about1,000,000, about 5,000 to about 800,000, about 5,000 to about 600,000,about 5,000 to about 400,000, about 5,000 to about 200,000, about 5,000to about 100,000, about 5,000 to about 80,000, about 5,000 to about75,000, about 5,000 to about 70,000, about 5,000 to about 65,000, about5,000 to about 60,000, about 5,000 to about 55,000, about 5,000 to about50,000, about 5,000 to about 45,000, about 5,000 to about 40,000, about5,000 to about 35,000, about 5,000 to about 30,000, about 5,000 to about25,000, about 5,000 to about 20,000, about 5,000 to about 15,000, about5,000 to about 10,000, about 5,000 to about 7,500, about 7,500 to about10,000,000, about 7,500 to about 9,000,000, about 7,500 to about8,000,000, about 7,500 to about 7,000,000, about 7,500 to about6,000,000, about 7,500 to about 5,000,000, about 7,500 to about4,000,000, about 7,500 to about 3,000,000, about 7,500 to about2,000,000, about 7,500 to about 1,000,000, about 7,500 to about 800,000,about 7,500 to about 600,000, about 7,500 to about 400,000, about 7,500to about 200,000, about 7,500 to about 100,000, about 7,500 to about80,000, about 7,500 to about 75,000, about 7,500 to about 70,000, about7,500 to about 65,000, about 7,500 to about 60,000, about 7,500 to about55,000, about 7,500 to about 50,000, about 7,500 to about 45,000, about7,500 to about 40,000, about 7,500 to about 35,000, about 7,500 to about30,000, about 7,500 to about 25,000, about 7,500 to about 20,000, about7,500 to about 15,000, about 7,500 to about 10,000, about 10,000 toabout 10,000,000, about 10,000 to about 9,000,000, about 10,000 to about8,000,000, about 10,000 to about 7,000,000, about 10,000 to about6,000,000, about 10.000 to about 5,000,000, about 10,000 to about4,000,000, about 10,000 to about 3,000,000, about 10,000 to about2,000,000, about 10,000 to about 1,000,000, about 10,000 to about800,000, about 10,000 to about 600,000, about 10,000 to about 400,000,about 10,000 to about 200,000, about 10,000 to about 100,000, about10,000 to about 80,000, about 10,000 to about 75,000, about 10,000 toabout 70,000, about 10,000 to about 65,000, about 10,000 to about60,000, about 10,000 to about 55,000, about 10,000 to about 50,000,about 10,000 to about 45,000, about 10,000 to about 40,000, about 10,000to about 35,000, about 10,000 to about 30,000, about 10,000 to about25,000, about 10,000 to about 20,000, about 10,000 to about 15,000,about 15,000 to about 10,000,000, about 15,000 to about 9,000,000, about15,000 to about 8,000,000, about 15,000 to about 7,000,000, about 15,000to about 6,000,000, about 15,000 to about 5,000,000, about 15,000 toabout 4,000,000, about 15,000 to about 3,000,000, about 15,000 to about2,000,000, about 15,000 to about 1,000,000, about 15,000 to about800,000, about 15,000 to about 600,000, about 15,000 to about 400,000,about 15,000 to about 200,000, about 15,000 to about 100,000, about15,000 to about 80,000, about 15,000 to about 75,000, about 15,000 toabout 70,000, about 15,000 to about 65,000, about 15,000 to about60,000, about 15,000 to about 55,000, about 15,000 to about 50,000,about 15,000 to about 45,000, about 15,000 to about 40,000, about 15,000to about 35,000, about 15,000 to about 30,000, about 15,000 to about25,000, about 15,000 to about 20,000, about 20,000 to about 10,000,000,about 20,000 to about 9,000,000, about 20,000 to about 8,000,000, about20,000 to about 7,000,000, about 20,000 to about 6,000,000, about 20,000to about 5,000,000, about 20,000 to about 4,000,000, about 20,000 toabout 3,000,000, about 20,000 to about 2,000,000, about 20,000 to about1,000,000, about 20,000 to about 800,000, about 20,000 to about 600,000,about 20,000 to about 400,000, about 20,000 to about 200,000, about20,000 to about 100,000, about 20,000 to about 80,000, about 20,000 toabout 75,000, about 20,000 to about 70,000, about 20,000 to about65,000, about 210,000 to about 60,000, about 20,000 to about 55,000,about 20,000 to about 50,000, about 20.000 to about 45,000, about 20,000to about 40,000, about 20,000 to about 35,000, about 20.000 to about30,000, about 20,000 to about 25,000, about 25,000 to about 10,000,000,about 25,000 to about 9,000,000, about 25,000 to about 8,000,000, about25,000 to about 7,000,000, about 25,000 to about 6,000,000, about 25,000to about 5,000,000, about 25,000 to about 4,000,000, about 25,000 toabout 3,000,000, about 25,000 to about 2,000,000, about 25,000 to about1,000,000, about 25,000 to about 800,000, about 25,000 to about 600,000,about 25,000 to about 400,000, about 25,000 to about 200,000, about25,000 to about 100,000, about 25,000 to about 80,000, about 25,000 toabout 75,000, about 25,000 to about 70,000, about 25,000 to about65,000, about 25,000 to about 60,000, about 25,000 to about 55,000,about 25,000 to about 50,000, about 25,000 to about 45,000, about 25,000to about 40,000, about 25,000 to about 35,000, about 25,000 to about30,000, about 30,000 to about 10,000,000, about 30,000 to about9,000,000, about 30,000 to about 8,000,000, about 30,000 to about7,000,000, about 30,000 to about 6,000,000, about 30,000 to about5,000,000, about 30,000 to about 4,000,000, about 30,000 to about3,000,000, about 30,000 to about 2,000,000, about 30,000 to about1,000,000, about 30,000 to about 800,000, about 30,000 to about 600,000,about 30,000 to about 400,000, about 30,000 to about 200,000, about30,000 to about 100,000, about 30,000 to about 80,000, about 30,000 toabout 75,000, about 30,000 to about 70,000, about 30,000 to about65,000, about 30,000 to about 60,000, about 30,000 to about 55,000,about 30,000 to about 50,000, about 30,000 to about 45,000, about 30,000to about 40,000, about 30,000 to about 35,000, about 35,000 to about10,000,000, about 35,000 to about 9,000,000, about 35,000 to about8,000,000, about 35,000 to about 7,000,000, about 35,000 to about6,000,000, about 35,000 to about 5,000,000, about 35,000 to about4,000,000, about 35,000 to about 3,000,000, about 35,000 to about2,000,000, about 35,000 to about 1,000,000, about 35,000 to about800,000, about 35,000 to about 600,000, about 35,000 to about 400,000,about 35,000 to about 200,000, about 35,000 to about 100,000, about35,000 to about 80,000, about 35,000 to about 75,000, about 35,000 toabout 70,000, about 35,000 to about 65,000, about 35,000 to about60,000, about 35,000 to about 55,000, about 35,000 to about 50,000,about 35,000 to about 45,000, about 35,000 to about 40,000, about 40,000to about 10,000,000, about 40,000 to about 9,000,000, about 40,000 toabout 8,000,000, about 40,000 to about 7,000,000, about 40,000 to about6,000,000, about 40,000 to about 5,000,000, about 40,000 to about4,000,000, about 40,000 to about 3,000,000, about 40,000 to about2,000,000, about 40,000 to about 1,000,000, about 40,000 to about800,000, about 40,000 to about 600,000, about 40,000 to about 400,000,about 40,000 to about 200,000, about 40,000 to about 100,000, about40,000 to about 80,000, about 40,000 to about 75,000, about 40,000 toabout 70.000, about 40,000 to about 65,000, about 40,000 to about60,000, about 40,000 to about 55,000, about 40,000 to about 50,000,about 40,000 to about 45,000, about 45,000 to about 10,000,000, about45,000 to about 9,000,000, about 45,000 to about 8,000,000, about 45,000to about 7,000,000, about 45,000 to about 6,000,000, about 45,000 toabout 5,000,000, about 45,000 to about 4,000,000, about 45,000 to about3,000,000, about 45,000 to about 2,000,000, about 45,000 to about1,000,000, about 45,000 to about 800,000, about 45,000 to about 600,000,about 45,000 to about 400,000, about 45,000 to about 200,000, about45,000 to about 100,000, about 45,000 to about 80,000, about 45,000 toabout 75,000, about 45,000 to about 70,000, about 45,000 to about65,000, about 45,000 to about 60.000, about 45,000 to about 55,000,about 45,000 to about 50,000, about 50,000 to about 10,000,000, about50,000 to about 9,000,000, about 50,000 to about 8,000,000, about 50,000to about 7,000,000, about 50,000 to about 6,000,000, about 50,000 toabout 5,000,000, about 50,000 to about 4,000,000, about 50,000 to about3,000,000, about 50,000 to about 2,000,000, about 50,000 to about1,000,000, about 50,000 to about 800,000, about 50,000 to about 600,000,about 50,000 to about 400,000, about 50,000 to about 200,000, about50,000 to about 100,000, about 50,000 to about 80,000, about 50,000 toabout 75,000, about 50,000 to about 70,000, about 50,000 to about65,000, about 50,000 to about 60,000, about 50,000 to about 55,000,about 55,000 to about 10,000,000, about 55,000 to about 9,000,000, about55,000 to about 8,000,000, about 55,000 to about 7,000,000, about 55,000to about 6,000,000, about 55,000 to about 5,000,000, about 55,000 toabout 4,000,000, about 55,000 to about 3,000,000, about 55,000 to about2,000,000, about 55,000 to about 1,000,000, about 55,000 to about800,000, about 55,000 to about 600,000, about 55,000 to about 400,000,about 55,000 to about 200,000, about 55,000 to about 100,000, about55,000 to about 80,000, about 55,000 to about 75,000, about 55,000 toabout 70,000, about 55,000 to about 65,000, about 55,000 to about60,000, about 60,000 to about 10,000,000, about 60,000 to about9,000,000, about 60,000 to about 8,000,000, about 60,000 to about7,000,000, about 60,000 to about 6,000,000, about 60,000 to about5,000,000, about 60,000 to about 4,000,000, about 60,000 to about3,000,000, about 60,000 to about 2,000,000, about 60,000 to about1,000,000, about 60,000 to about 800,000, about 60,000 to about 600,000,about 60,000 to about 400,000, about 60,000 to about 200,000, about60,000 to about 100,000, about 60,000 to about 80,000, about 60,000 toabout 75,000, about 60,000 to about 70,000, about 60,000 to about65,000, about 65,000 to about 10,000,000, about 65,000 to about9,000,000, about 65,000 to about 8,000,000, about 65,000 to about7,000,000, about 65,000 to about 6,000,000, about 65,000 to about5,000,000, about 65,000 to about 4,000,000, about 65,000 to about3,000,000, about 65,000 to about 2,000,000, about 65,000 to about1,000,000, about 65,000 to about 800,000, about 65,000 to about 600,000,about 65,000 to about 400,000, about 65,000 to about 200,000, about65,000 to about 100,000, about 65,000 to about 80,000, about 65,000 toabout 75,000, about 65,000 to about 70,000, about 70,000 to about10,000,000, about 70,000 to about 9,000,000, about 70,000 to about8,000,000, about 70,000 to about 7,000,000, about 70,000 to about6,000,000, about 70,000 to about 5,000,000, about 70,000 to about4,000,000, about 70,000 to about 3,000,000, about 70,000 to about2,000,000, about 70,000 to about 1,000,000, about 70,000 to about800,000, about 70,000 to about 600,000, about 70,000 to about 400,000,about 70,000 to about 200,000, about 70,000 to about 100,000, about70,000 to about 90,000, about 70,000 to about 80,000, about 80,000 toabout 10,000,000, about 80,000 to about 9,000,000, about 80,000 to about8,000,000, about 80,000 to about 7,000,000, about 80,000 to about6,000,000, about 80,000 to about 5,000,000, about 80,000 to about4,000,000, about 80,000 to about 3,000,000, about 80,000 to about2,000,000, about 80,000 to about 1,000,000, about 80,000 to about800,000, about 80,000 to about 600,000, about 80,000 to about 400,000,about 80,000 to about 200,000, about 80,000 to about 100,000, about80,000 to about 90,000, about 90,000 to about 10,000,000, about 90,000to about 9,000,000, about 90,000 to about 8,000,000, about 90,000 toabout 7,000,000, about 90,000 to about 6,000,000, about 90,000 to about5,000,000, about 90,000 to about 4,000,000, about 90,000 to about3,000,000, about 90,000 to about 2,000,000, about 90,000 to about1,000,000, about 90,000 to about 800,000, about 90,000 to about 600,000,about 90,000 to about 400,000, about 90,000 to about 200,000, about90,000 to about 100,000, about 100,000 to about 10,000,000, about100,000 to about 9,000,000, about 100,000 to about 8,000,000, about100,000 to about 7,000,000, about 100,000 to about 6,000,000, about100,000 to about 5,000,000, about 100,000 to about 4,000,000, about100,000 to about 3,000,000, about 100,000 to about 2,000,000, about100,000 to about 1,000,000, about 100,000 to about 800,000, about100,000 to about 600,000, about 100,000 to about 400,000, about 100,000to about 200,000, about 200,000 to about 10,000,000, about 200,000 toabout 9,000,000, about 200,000 to about 8,000,000, about 200,000 toabout 7,000,000, about 200,000 to about 6,000,000, about 200,000 toabout 5,000,000, about 200,000 to about 4,000,000, about 200,000 toabout 3,000,000, about 200,000 to about 2,000,000, about 200,000 toabout 1,000,000, about 200,000 to about 800,000, about 200,000 to about600,000, about 200,000 to about 400,000, about 400,000 to about10,000,000, about 400,000 to about 9,000,000, about 400,000 to about8,000,000, about 400,000 to about 7,000,000, about 400,000 to about6,000,000, about 400,000 to about 5,000,000, about 400,000 to about4,000,000, about 400,000 to about 3,000,000, about 400,000 to about2,000,000, about 400,000 to about 1,000,000, about 400,000 to about800,000, about 400,000 to about 600,000, about 600,000 to about10,000,000, about 600,000 to about 9,000,000, about 600,000 to about8,000,000, about 600,000 to about 7,000,000, about 600,000 to about6,000,000, about 600,000 to about 5,000,000, about 600,000 to about4,000,000, about 600,000 to about 3,000,000, about 600,000 to about2,000,000, about 600,000 to about 1,000,000, about 600,000 to about800,000, about 800,000 to about 10,000,000, about 800,000 to about9,000,000, about 800,000 to about 8,000,000, about 800,000 to about7,000,000, about 800,000 to about 6,000,000, about 800,000 to about5,000,000, about 800,000 to about 4,000,000, about 800,000 to about3,000,000, about 800,000 to about 2,000,000, about 800,000 to about1,000,000, about 1,000,000 to about 10,000,000, about 1,000,000 to about9,000,000, about 1,000,000 to about 8,000,000, about 1,000,000 to about7,000,000, about 1,000,000 to about 6,000,000, about 1,000,000 to about5,000,000, about 1,000,000 to about 4,000,000, about 1,000,000 to about3,000,000, about 1,000,000 to about 2,000,000, about 2,000,000 to about10,000,000, about 2,000,000 to about 9,000,000, about 2,000,000 to about8,000,000, about 2,000,000 to about 7,000,000, about 2,000,000 to about6,000,000, about 2,000,000 to about 5,000,000, about 2,000,000 to about4,000,000, about 2,000,000 to about 3,000,000, about 3,000,000 to about10,000,000, about 3,000,000 to about 9,000,000, about 3,000,000 to about8,000,000, about 3,000,000 to about 7,000,000, about 3,000,000 to about6,000,000, about 3,000,000 to about 5,000,000, about 3,000,000 to about4,000,000, about 4,000,000 to about 10,000,000, about 4,000,000 to about9,000,000, about 4,000,000 to about 8,000,000, about 4,000,000 to about7,000,000, about 4,000,000 to about 6,000,000, about 4,000,000 to about5,000,000, about 5,000,000 to about 10,000,000, about 5,000,000 to about9,000,000, about 5,000,000 to about 8,000,000, about 5,000,000 to about7,000,000, about 5,000,000 to about 6,000,000, about 6,000,000 to about10,000,000, about 6,000,000 to about 9,000,000, about 6,000,000 to about8,000,000, about 6,000,000 to about 7,000,000, about 7,000,000 to about10,000,000, about 7,000,000 to about 9,000,000, about 7,000,000 to about8,000,000, about 8,000,000 to about 10,000,000, about 8,000,000 to about9,000,000, or about 9,000,000 to about 10,000,000 of the FOLR1 onpresent on the plasma membrane of the target mammalian cell.

The phrase “antigen density” means the number of FOLR1 present on thesurface of a target mammalian cell or the average number of FOLR1 on thesurface of a population of particular type of target mammalian cells. Itcan be measured, e.g., using the Quantibright bead kit or radiolabel(e.g., BD Biosciences PE Phycoerythrin Fluorescence Quantitation Kit,catalog #340495).

The phrase “amino acid substituted with a histidine” means thesubstitution of an amino acid residue that is not histidine in areference polypeptide sequence with a histidine. Non-limiting methodsfor substituting an amino acid residue in a reference polypeptide with ahistidine are described herein. Additional methods for substituting anamino acid residue in a reference polypeptide with a histidine are knownin the art.

The phrase “amino acid substituted with an alanine” means thesubstitution of an amino acid residue that is a histidine in a referencepolypeptide sequence with an alanine. Non-limiting methods forsubstituting a histidine in a reference polypeptide with an alanine aredescribed herein. Additional methods for substituting a histidine in areference polypeptide with an alanine are known in the art.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Methods and materials aredescribed herein for use in the present invention; other, suitablemethods and materials known in the art can also be used. The materials,methods, and examples are illustrative only and not intended to belimiting. All publications, patent applications, patents, sequences,database entries, and other references mentioned herein are incorporatedby reference in their entirety. In case of conflict, the presentspecification, including definitions, will control.

Other features and advantages of the invention will be apparent from thefollowing detailed description and figures, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1: SDS PAGE for MIRVETUXIMAB histidine scanning and alaninescanning. Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of MIRVETUXIMAB andhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel. MYT0596 isMIRVETUXIMAB and the rest of the lanes (MYT0597-MYT0637) areMIRVETUXIMAB heavy chain histidine scanning and alanine scanningvariants.

FIGS. 2a to 2 ap: Binding of MIRVETUXIMAB starting ABPC and histidinescanning and alanine scanning variants to FOLR1 by biolayerinterferometry. MYT0596 (MIRVETUXIMAB) and MYT0597-MYT0637, heavy chainhistidine scanning and alanine scanning variants, were captured onanti-human Fc biosensors and associated with FOLR1 at low pH or high pH,as specified in the figures.

FIG. 3: Construct identifier to SEQ ID NO correspondence table.Constructs, heavy chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 4: SDS PAGE for MIRVETUXIMAB histidine scanning and alaninescanning. Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of MIRVETUXIMABhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel.MYT1559-MYT1589 are MIRVETUXIMAB light chain histidine scanning andalanine scanning variants.

FIGS. 5a to 5 ae: Binding of MIRVETUXIMAB histidine scanning and alaninescanning variants to FOLR1 by biolayer interferometry. MYT1559-MYT1589,light chain histidine scanning and alanine scanning variants, werecaptured on anti-human Fc biosensors and associated with FOLR1 at low pHor high pH, as specified in the figures.

FIG. 6: Construct identifier to SEQ ID NO correspondence table.Constructs, light chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 7: SDS PAGE for MIRVETUXIMAB histidine scanning and alaninescanning. Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of MIRVETUXIMABhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel.MYT1142-MYT1161 are MIRVETUXIMAB heavy chain combinations histidinescanning and alanine scanning variants.

FIGS. 8a to 8t : Binding of histidine scanning and alanine scanningvariants of MIRVETUXIMAB to FOLR1 by biolayer interferometry.MYT1142-MYT1161, heavy chain combinations histidine scanning and alaninescanning variants, were captured on anti-human Fc biosensors andassociated with FOLR1 at low pH or high pH, as specified in the figures.

FIG. 9: Construct identifier to SEQ ID NO correspondence table.Constructs, heavy chain combinations histidine scanning and alaninescanning variants, are listed in the first column of the table, SEQ IDNOs are listed and correspond to constructs on the left and theappropriate heavy chain, light chain, and CDR categories along the top.

FIG. 10: SDS PAGE for STRO-002 histidine scanning and alanine scanning.Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of STRO-002 andhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel. MYT2224 isSTRO-002 and the rest of the lanes (MYT2225-MYT2268) are STRO-002 heavychain histidine scanning and alanine scanning variants.

FIGS. 11a to 11 as: Binding of STRO-002 starting ABPC and histidinescanning and alanine scanning variants to FOLR1 by biolayerinterferometry. MYT2224 (STRO-002) and MYT2225-MYT2268, heavy chainhistidine scanning and alanine scanning variants, were captured onanti-human Fc biosensors and associated with FOLR1 at low pH or high pH,as specified in the figures.

FIG. 12: Construct identifier to SEQ ID NO correspondence table.Constructs, heavy chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 13: SDS PAGE for STRO-002 histidine scanning and alanine scanning.Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of STRO-002 histidinescanning and alanine scanning variants. Arrows show the correspondingsize for an IgG on a non-reduced SDS PAGE gel. MYT4493-MYT4519 areSTRO-002 light chain histidine scanning and alanine scanning variants.

FIGS. 14a to 14 aa: Binding of STRO-002 histidine scanning and alaninescanning variants to FOLR1 by biolayer interferometry. MYT4493-MYT4519,light chain histidine scanning and alanine scanning variants, werecaptured on anti-human Fc biosensors and associated with FOLR1 at low pHor high pH, as specified in the figures.

FIG. 15: Construct identifier to SEQ ID NO correspondence table.Constructs, light chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 16: SDS PAGE for FARLETUZUMAB histidine scanning and alaninescanning. Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of FARLETUZUMAB andhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel. MYT2184 isFARLETUZUMAB and the rest of the lanes (MYT2185-MYT2223) areFARLETUZUMAB heavy chain histidine scanning and alanine scanningvariants.

FIGS. 17a to 17 an: Binding of FARLETUZUMAB starting ABPC and histidinescanning and alanine scanning variants to FOLR1 by biolayerinterferometry. MYT2184 (FARLETUZUMAB) and MYT2185-MYT2223, heavy chainhistidine scanning and alanine scanning variants, were captured onanti-human Fc biosensors and associated with FOLR1 at low pH or high pH,as specified in the figures.

FIG. 18: Construct identifier to SEQ ID NO correspondence table.Constructs, heavy chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 19: SDS PAGE for FARLETUZUMAB histidine scanning and alaninescanning. Expi293 cell culture supernatants post-harvest were loaded onnon-reduced SDS PAGE gels to confirm expression of FARLETUZUMABhistidine scanning and alanine scanning variants. Arrows show thecorresponding size for an IgG on a non-reduced SDS PAGE gel.MYT4520-MYT4546 are FARLETUZUMAB light chain histidine scanning andalanine scanning variants.

FIGS. 20a to 20 aa: Binding of FARLETUZUMAB histidine scanning andalanine scanning variants to FOLR1 by biolayer interferometry.MYT4520-MYT4546, light chain histidine scanning and alanine scanningvariants, were captured on anti-human Fc biosensors and associated withFOLR1 at low pH or high pH, as specified in the figures.

FIG. 21: Construct identifier to SEQ ID NO correspondence table.Constructs, light chain histidine scanning and alanine scanningvariants, are listed in the first column of the table, SEQ ID NOs arelisted and correspond to constructs on the left and the appropriateheavy chain, light chain, and CDR categories along the top.

FIG. 22: Internalization of anti-FOLR1 mAbs in NIH:OVCAR-3 cells.Anti-FOLR1 pH engineered antibody variants, corresponding starting ABPCantibodies, control IgG1 isotype control (BP0297, Bioxcell), along witha vehicle control, as specified in FIG. 22 were assayed forinternalization and endolysosomal delivery as measured by meanfluorescence intensity on NIH:OVCAR-3 cells at 24 hours. Error barsrepresent standard deviation. Numbers above the bars represent foldchange over wild-type.

FIGS. 23a-23c : Characterization of binding affinity for anti-FOLR1mAbs. Anti-FOLR1 mA bs were assayed for their binding to NIH:OVCAR-3cells. FIG. 23a shows mirvetuximab with an IC50 of 0.250 nM, FIG. 23bshows MYT0603 with an IC50 of 0.650 nM, FIG. 23c shows MYT1154 with anIC50 of 0.396 nM.

FIG. 24: Melting temperature of select anti-FOLR1 mAbs. Mirvetuximab(MYT0596) and histidine and alanine scanning variants were assayed fortheir melting temperature by Differential Scanning Flourimetry (DSF),and the resulting Sypro Orange signal was plotted as its firstderivative. Melting temperature (Tm) was calculated as the local maximaof this graph and listed in the table as shown. Constructs are listed inthe first column of the table, Tm 1, and if applicable (for example, ifthe graph had two local maxima), Tm 2, are listed in the second andthird columns, respectively.

DETAILED DESCRIPTION

Provided herein are antigen-binding protein constructs (ABPCs) thatinclude: a first antigen-binding domain that is capable of specificallybinding FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, where: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; and/or (b) thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0. In some examples of these ABPCs, the ABPC is degraded in thetarget mammalian cell following internalization of the ABPC by thetarget mammalian cell. Some examples of any of the ABPCs describedherein can further include a conjugated toxin, radioisotope, drug, orsmall molecule (e.g., a fluorophore or dye).

Also provided are antigen-binding protein constructs (ABPCs) thatinclude: a first antigen-binding domain that is capable of specificallybinding FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell; and a conjugated toxin, radioisotope, drug, orsmall molecule, where: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; and/or thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the K_(D) at a pH of about 7.0to about 8.0; and (b) a composition including the ABPC provides for oneor more (e.g., two or three) of: an increase (e.g., a detectableincrease) in toxin liberation in the target mammalian cell as comparedto a composition comprising the same amount of a control ABPC; anincrease (e.g., a detectable increase) in target mammalian cell killingas compared to a composition comprising the same amount of a controlABPC; and an increase (e.g., a detectable increase) in endolysosomaldelivery in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain ofmirvetuximab with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) amino acidssubstituted with a histidine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of mirvetuximab with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acids substituted with a histidine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of mirvetuximab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acids substituted with a histidine;and a light chain variable domain of mirvetuximab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acids substituted with a histidine.In some examples of any of the ABPCs described herein, the heavy chainvariable domain of mirvetuximab comprises SEQ ID NO: 1. In some examplesof any of the ABPCs described herein, the light chain variable domain ofmirvetuximab comprises SEQ ID NO: 2.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, andSEQ ID NO: 5, respectively, with collectively a total of one or more(e.g., one, two, three, four, five, six, seven, eight, nine, or ten)amino acid positions in SEQ ID NOs: 3-5 substituted with a histidine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, andSEQ ID NO: 8, respectively, with collectively a total of one or more(e.g., one, two, three, four, five; six, seven, eight, nine, or ten)amino acid positions in SEQ ID NOs: 6-8 substituted with a histidine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain includes: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, andSEQ ID NO: 5, respectively, with collectively a total of one or more(e.g., one, two, three, four, five, six, seven, eight, nine, or ten)amino acid positions in SEQ ID NOs: 3-5 substituted with a histidine;and a light chain variable domain comprising a CDR1, a CDR2, and a CDR3of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8, respectively, withcollectively a total of one or more (e.g., one, two, three, four, five,six, seven, eight; nine, or ten) amino acid positions in SEQ ID NOs: 6-8substituted with a histidine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%; at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at one or more (e.g., one, two,three, four, five; six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 1 selected from the groupconsisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60,97, 98, 99, 100, 102, 103, 105, and 107. In some examples of any of theABPCs described herein, the first antigen-binding domain includes alight chain variable domain that is at least 90% (e.g., at least 92%, atleast 94%, at least 96%, at least 98%, at least 99%, or 100%) identicalto SEQ ID NO: 2, where the light chain variable domain includes ahistidine at one or more (e.g., one, two, three, four, five, six, seven,eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 2 selected from the group consisting of: 28, 30, 31; 32, 34, 35, 36,55, 59, 93, 94, 95, 96, 97, 98; and 100. In some examples of any of theABPCs described herein the first antigen-binding domain includes: aheavy chain variable domain that is at least 90% (e.g., at least 92%, atleast 94%, at least 96%, at least 98%, at least 99%, or 100%) identicalto SEQ ID NO: 1, where the heavy chain variable domain includes ahistidine at one or more (e.g., one, two, three, four, five, six, seven,eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34,50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107, anda light chain variable domain that is at least 90% (e.g., at least 92%,at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 2, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 2 selected from the group consisting of: 28, 30,31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes an alanine at position 52 in SEQ ID NO: 1.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a heavy chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavychain variable domain includes an alanine at position 52 in SEQ ID NO:1, and a light chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 2, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 2 selected from the group consisting of: 28, 30,31, 32, 34, 35, 36; 38, 55, 59, 93, 94, 95, 96, 97, 98, and 100.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 1 selected from the groupconsisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60,97, 98, 99, 100, 102, 103, 105, and 107, and where the heavy chainvariable domain includes an alanine at position 52 in SEQ ID NO: 1. Insome examples of any of the ABPCs described herein the firstantigen-binding domain includes: a heavy chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavychain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 1 selected from the groupconsisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60,97, 98, 99, 100, 102, 103, 105, and 107, and where the heavy chainvariable domain includes an alanine at position 52 in SEQ ID NO: 100,and a light chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 2, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 2 selected from the group consisting of: 28, 30,31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 1 listed in Table 1and where the heavy chain variable domain includes an alanine atposition 52 of SEQ ID NO: 1.

TABLE 1 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 1that can be Substituted with Histidine 24 + 27, 24 + 29, 24 + 31, 24 +32, 24 + 33, 24 + 34, 24 + 50, 24 + 54, 24 + 55, 24 + 57, 24 + 58, 24 +59, 24 + 60, 24 + 97, 24 + 98, 24 + 99, 24 + 100, 24 + 102, 24 + 103,24 + 105, 24 + 107, 27 + 29, 27 + 31, 27 + 32, 27 + 33, 27 + 34, 27 +50, 27 + 54, 27 + 55, 27 + 57, 27 + 58, 27 + 59, 27 + 60, 27 + 97, 27 +98, 27 + 99, 27 + 100, 27 + 102, 27 + 103, 27 + 105, 27 + 107, 29 + 31,29 + 32, 29 + 33, 29 + 34, 29 + 50, 29 + 54, 29 + 55, 29 + 57, 29 + 58,29 + 59, 29 + 60, 29 + 97, 29 + 98, 29 + 99, 29 + 100, 29 + 102, 29 +103, 29 + 105, 29 + 107, 31 + 32, 31 + 33, 31 + 34, 31 + 50, 31 + 54,31 + 55, 31 + 57, 31 + 58, 31 + 59, 31 + 60, 31 + 97, 31 + 98, 31 + 99,31 + 100, 31 + 102, 31 + 103, 31 + 105, 31 + 107, 32 + 33, 32 + 34, 32 +50, 32 + 54, 32 + 55, 32 + 57, 32 + 58, 32 + 59, 32 + 60, 32 + 97, 32 +98, 32 + 99, 32 + 100, 32 + 102, 32 + 103, 32 + 105, 32 + 107, 33 + 34,33 + 50, 33 + 54, 33 + 55, 33 + 57, 33 + 58, 33 + 59, 33 + 60, 33 + 97,33 + 98, 33 + 99, 33 + 100, 33 + 102, 33 + 103, 33 + 105, 33 + 107, 34 +50, 34 + 54, 34 + 55, 34 + 57, 34 + 58, 34 + 59, 34 + 60, 34 + 97, 34 +98, 34 + 99, 34 + 100, 34 + 102, 34 + 103, 34 + 105, 34 + 107, 50 + 54,50 + 55, 50 + 57, 50 + 58, 50 + 59, 50 + 60, 50 + 97, 50 + 98, 50 + 99,50 + 100, 50 + 102, 50 + 103, 50 + 105, 50 + 107, 54 + 55, 54 + 57, 54 +58, 54 + 59, 54 + 60, 54 + 97, 54 + 98, 54 + 99, 54 + 100, 54 + 102,54 + 103, 54 + 105, 54 + 107, 55 + 57, 55 + 58, 55 + 59, 55 + 60, 55 +97, 55 + 98, 55 + 99, 55 + 100, 55 + 102, 55 + 103, 55 + 105, 55 + 107,57 + 58, 57 + 59, 57 + 60, 57 + 97, 57 + 98, 57 + 99, 57 + 100, 57 +102, 57 + 103, 57 + 105, 57 + 107, 58 + 59, 58 + 60, 58 + 97, 58 + 98,58 + 99, 58 + 100, 58 + 102, 58 + 103, 58 + 105, 58 + 107, 59 + 60, 59 +97, 59 + 98, 59 + 99, 59 + 100, 59 + 102, 59 + 103, 59 + 105, 59 + 107,60 + 97, 60 + 98, 60 + 99, 60 + 100, 60 + 102, 60 + 103, 60 + 105, 60 +107, 97 + 98, 97 + 99, 97 + 100, 97 + 102, 97 + 103, 97 + 105, 97 + 107,98 + 99, 98 + 100, 98 + 102, 98 + 103, 98 + 105, 98 + 107, 99 + 100,99 + 102, 99 + 103, 99 + 105, 99 + 107, 100 + 102, 100 + 103, 100 + 105,100 + 107, 102 + 103, 102 + 105, 102 + 107, 103 + 105, 103 + 107, 105 +107, 24 + 27 + 29, 24 + 27 + 31, 24 + 27 + 32, 24 + 27 + 33, 24 + 27 +34, 24 + 27 + 50, 24 + 27 + 54, 24 + 27 + 55, 24 + 27 + 57, 24 + 27 +58, 24 + 27 + 59, 24 + 27 + 60, 24 + 27 + 97, 24 + 27 + 98, 24 + 27 +99, 24 + 27 + 100, 24 + 27 + 102, 24 + 27 + 103, 24 + 27 + 105, 24 +27 + 107, 24 + 29 + 31, 24 + 29 + 32, 24 + 29 + 33, 24 + 29 + 34, 24 +29 + 50, 24 + 29 + 54, 24 + 29 + 55, 24 + 29 + 57, 24 + 29 + 58, 24 +29 + 59, 24 + 29 + 60, 24 + 29 + 97, 24 + 29 + 98, 24 + 29 + 99, 24 +29 + 100, 24 + 29 + 102, 24 + 29 + 103, 24 + 29 + 105, 24 + 29 + 107,24 + 31 + 32, 24 + 31 + 33, 24 + 31 + 34, 24 + 31 + 50, 24 + 31 + 54,24 + 31 + 55, 24 + 31 + 57, 24 + 31 + 58, 24 + 31 + 59, 24 + 31 + 60,24 + 31 + 97, 24 + 31 + 98, 24 + 31 + 99, 24 + 31 + 100, 24 + 31 + 102,24 + 31 + 103, 24 + 31 + 105, 24 + 31 + 107, 24 + 32 + 33, 24 + 32 + 34,24 + 32 + 50, 24 + 32 + 54, 24 + 32 + 55, 24 + 32 + 57, 24 + 32 + 58,24 + 32 + 59, 24 + 32 + 60, 24 + 32 + 97, 24 + 32 + 98, 24 + 32 + 99,24 + 32 + 100, 24 + 32 + 102, 24 + 32 + 103, 24 + 32 + 105, 24 + 32 +107, 24 + 33 + 34, 24 + 33 + 50, 24 + 33 + 54, 24 + 33 + 55, 24 + 33 +57, 24 + 33 + 58, 24 + 33 + 59, 24 + 33 + 60, 24 + 33 + 97, 24 + 33 +98, 24 + 33 + 99, 24 + 33 + 100, 24 + 33 + 102, 24 + 33 + 103, 24 + 33 +105, 24 + 33 + 107, 24 + 34 + 50, 24 + 34 + 54, 24 + 34 + 55, 24 + 34 +57, 24 + 34 + 58, 24 + 34 + 59, 24 + 34 + 60, 24 + 34 + 97, 24 + 34 +98, 24 + 34 + 99, 24 + 34 + 100, 24 + 34 + 102, 24 + 34 + 103, 24 + 34 +105, 24 + 34 + 107, 24 + 50 + 54, 24 + 50 + 55, 24 + 50 + 57, 24 + 50 +58, 24 + 50 + 59, 24 + 50 + 60, 24 + 50 + 97, 24 + 50 + 98, 24 + 50 +99, 24 + 50 + 100, 24 + 50 + 102, 24 + 50 + 103, 24 + 50 + 105, 24 +50 + 107, 24 + 54 + 55, 24 + 54 + 57, 24 + 54 + 58, 24 + 54 + 59, 24 +54 + 60, 24 + 54 + 97, 24 + 54 + 98, 24 + 54 + 99, 24 + 54 + 100, 24 +54 + 102, 24 + 54 + 103, 24 + 54 + 105, 24 + 54 + 107, 24 + 55 + 57,24 + 55 + 58, 24 + 55 + 59, 24 + 55 + 60, 24 + 55 + 97, 24 + 55 + 98,24 + 55 + 99, 24 + 55 + 100, 24 + 55 + 102, 24 + 55 + 103, 24 + 55 +105, 24 + 55 + 107, 24 + 57 + 58, 24 + 57 + 59, 24 + 57 + 60, 24 + 57 +97, 24 + 57 + 98, 24 + 57 + 99, 24 + 57 + 100, 24 + 57 + 102, 24 + 57 +103, 24 + 57 + 105, 24 + 57 + 107, 24 + 58 + 59, 24 + 58 + 60, 24 + 58 +97, 24 + 58 + 98, 24 + 58 + 99, 24 + 58 + 100, 24 + 58 + 102, 24 + 58 +103, 24 + 58 + 105, 24 + 58 + 107, 24 + 59 + 60, 24 + 59 + 97, 24 + 59 +98, 24 + 59 + 99, 24 + 59 + 100, 24 + 59 + 102, 24 + 59 + 103, 24 + 59 +105, 24 + 59 + 107, 24 + 60 + 97, 24 + 60 + 98, 24 + 60 + 99, 24 + 60 +100, 24 + 60 + 102, 24 + 60 + 103, 24 + 60 + 105, 24 + 60 + 107, 24 +97 + 98, 24 + 97 + 99, 24 + 97 + 100, 24 + 97 + 102, 24 + 97 + 103, 24 +97 + 105, 24 + 97 + 107, 24 + 98 + 99, 24 + 98 + 100, 24 + 98 + 102,24 + 98 + 103, 24 + 98 + 105, 24 + 98 + 107, 24 + 99 + 100, 24 + 99 +102, 24 + 99 + 103, 24 + 99 + 105, 24 + 99 + 107, 24 + 100 + 102, 24 +100 + 103, 24 + 100 + 105, 24 + 100 + 107, 24 + 102 + 103, 24 + 102 +105, 24 + 102 + 107, 24 + 103 + 105, 24 + 103 + 107, 24 + 105 + 107,27 + 29 + 31, 27 + 29 + 32, 27 + 29 + 33, 27 + 29 + 34, 27 + 29 + 50,27 + 29 + 54, 27 + 29 + 55, 27 + 29 + 57, 27 + 29 + 58, 27 + 29 + 59,27 + 29 + 60, 27 + 29 + 97, 27 + 29 + 98, 27 + 29 + 99, 27 + 29 + 100,27 + 29 + 102, 27 + 29 + 103, 27 + 29 + 105, 27 + 29 + 107, 27 + 31 +32, 27 + 31 + 33, 27 + 31 + 34, 27 + 31 + 50, 27 + 31 + 54, 27 + 31 +55, 27 + 31 + 57, 27 + 31 + 58, 27 + 31 + 59, 27 + 31 + 60, 27 + 31 +97, 27 + 31 + 98, 27 + 31 + 99, 27 + 31 + 100, 27 + 31 + 102, 27 + 31 +103, 27 + 31 + 105, 27 + 31 + 107, 27 + 32 + 33, 27 + 32 + 34, 27 + 32 +50, 27 + 32 + 54, 27 + 32 + 55, 27 + 32 + 57, 27 + 32 + 58, 27 + 32 +59, 27 + 32 + 60, 27 + 32 + 97, 27 + 32 + 98, 27 + 32 + 99, 27 + 32 +100, 27 + 32 + 102, 27 + 32 + 103, 27 + 32 + 105, 27 + 32 + 107, 27 +33 + 34, 27 + 33 + 50, 27 + 33 + 54, 27 + 33 + 55, 27 + 33 + 57, 27 +33 + 58, 27 + 33 + 59, 27 + 33 + 60, 27 + 33 + 97, 27 + 33 + 98, 27 +33 + 99, 27 + 33 + 100, 27 + 33 + 102, 27 + 33 + 103, 27 + 33 + 105,27 + 33 + 107, 27 + 34 + 50, 27 + 34 + 54, 27 + 34 + 55, 27 + 34 + 57,27 + 34 + 58, 27 + 34 + 59, 27 + 34 + 60, 27 + 34 + 97, 27 + 34 + 98,27 + 34 + 99, 27 + 34 + 100, 27 + 34 + 102, 27 + 34 + 103, 27 + 34 +105, 27 + 34 + 107, 27 + 50 + 54, 27 + 50 + 55, 27 + 50 + 57, 27 + 50 +58, 27 + 50 + 59, 27 + 50 + 60, 27 + 50 + 97, 27 + 50 + 98, 27 + 50 +99, 27 + 50 + 100, 27 + 50 + 102, 27 + 50 + 103, 27 + 50 + 105, 27 +50 + 107, 27 + 54 + 55, 27 + 54 + 57, 27 + 54 + 58, 27 + 54 + 59, 27 +54 + 60, 27 + 54 + 97, 27 + 54 + 98, 27 + 54 + 99, 27 + 54 + 100, 27 +54 + 102, 27 + 54 + 103, 27 + 54 + 105, 27 + 54 + 107, 27 + 55 + 57,27 + 55 + 58, 27 + 55 + 59, 27 + 55 + 60, 27 + 55 + 97, 27 + 55 + 98,27 + 55 + 99, 27 + 55 + 100, 27 + 55 + 102, 27 + 55 + 103, 27 + 55 +105, 27 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33, 29 + 31 + 34, 29 + 31 + 50, 29 + 31 + 54,29 + 31 + 55, 29 + 31 + 57, 29 + 31 + 58, 29 + 31 + 59, 29 + 31 + 60,29 + 31 + 97, 29 + 31 + 98, 29 + 31 + 99, 29 + 31 + 100, 29 + 31 + 102,29 + 31 + 103, 29 + 31 + 105, 29 + 31 + 107, 29 + 32 + 33, 29 + 32 + 34,29 + 32 + 50, 29 + 32 + 54, 29 + 32 + 55, 29 + 32 + 57, 29 + 32 + 58,29 + 32 + 59, 29 + 32 + 60, 29 + 32 + 97, 29 + 32 + 98, 29 + 32 + 99,29 + 32 + 100, 29 + 32 + 102, 29 + 32 + 103, 29 + 32 + 105, 29 + 32 +107, 29 + 33 + 34, 29 + 33 + 50, 29 + 33 + 54, 29 + 33 + 55, 29 + 33 +57, 29 + 33 + 58, 29 + 33 + 59, 29 + 33 + 60, 29 + 33 + 97, 29 + 33 +98, 29 + 33 + 99, 29 + 33 + 100, 29 + 33 + 102, 29 + 33 + 103, 29 + 33 +105, 29 + 33 + 107, 29 + 34 + 50, 29 + 34 + 54, 29 + 34 + 55, 29 + 34 +57, 29 + 34 + 58, 29 + 34 + 59, 29 + 34 + 60, 29 + 34 + 97, 29 + 34 +98, 29 + 34 + 99, 29 + 34 + 100, 29 + 34 + 102, 29 + 34 + 103, 29 + 34 +105, 29 + 34 + 107, 29 + 50 + 54, 29 + 50 + 55, 29 + 50 + 57, 29 + 50 +58, 29 + 50 + 59, 29 + 50 + 60, 29 + 50 + 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In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 2, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 2 listed in Table 2.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 2, where the light chainvariable domain includes an alanine at position 38 in SEQ ID NO: 2.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a light chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 2, where the lightchain variable domain includes an alanine at position 38 in SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 1, where the heavy chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102,103, 105, and 107.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 2, where the light chainvariable domain includes a histidine at one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 2 selected from the groupconsisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97,98, and 100 and where the light chain variable domain includes analanine at position 38 in SEQ ID NO: 2. In some examples of any of theABPCs described herein the first antigen-binding domain includes: alight chain variable domain that is at least 90% (e.g., at least 92%, atleast 94%, at least 96%, at least 98%, at least 99%, or 100%) identicalto SEQ ID NO: 2, where the light chain variable domain includes ahistidine at one or more (e.g., one, two, three, four, five, six, seven,eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 2 selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36,55, 59, 93, 94, 95, 96, 97, 98, and 100 and where the light chainvariable domain includes an alanine at position 38 in SEQ ID NO: 2, anda heavy chain variable domain that is at least 90% (e.g., at least 92%,at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 1, where the heavy chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102,103, 105, and 107.

In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 2, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 2 listed in Table 2and where the light chain variable domain includes an alanine atposition 38 of SEQ ID NO: 2.

TABLE 2 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 2that can be Substituted with Histidine 28 + 30, 28 + 31, 28 + 32, 28 +34, 28 + 35, 28 + 36, 28 + 55, 28 + 59, 28 + 93, 28 + 94, 28 + 95, 28 +96, 28 + 97, 28 + 98, 28 + 100, 30 + 31, 30 + 32, 30 + 34, 30 + 35, 30 +36, 30 + 55, 30 + 59, 30 + 93, 30 + 94, 30 + 95, 30 + 96, 30 + 97, 30 +98, 30 + 100, 31 + 32, 31 + 34, 31 + 35, 31 + 36, 31 + 55, 31 + 59, 31 +93, 31 + 94, 31 + 95, 31 + 96, 31 + 97, 31 + 98, 31 + 100, 32 + 34, 32 +35, 32 + 36, 32 + 55, 32 + 59, 32 + 93, 32 + 94, 32 + 95, 32 + 96, 32 +97, 32 + 98, 32 + 100, 34 + 35, 34 + 36, 34 + 55, 34 + 59, 34 + 93, 34 +94, 34 + 95, 34 + 96, 34 + 97, 34 + 98, 34 + 100, 35 + 36, 35 + 55, 35 +59, 35 + 93, 35 + 94, 35 + 95, 35 + 96, 35 + 97, 35 + 98, 35 + 100, 36 +55, 36 + 59, 36 + 93, 36 + 94, 36 + 95, 36 + 96, 36 + 97, 36 + 98, 36 +100, 55 + 59, 55 + 93, 55 + 94, 55 + 95, 55 + 96, 55 + 97, 55 + 98, 55 +100, 59 + 93, 59 + 94, 59 + 95, 59 + 96, 59 + 97, 59 + 98, 59 + 100,93 + 94, 93 + 95, 93 + 96, 93 + 97, 93 + 98, 93 + 100, 94 + 95, 94 + 96,94 + 97, 94 + 98, 94 + 100, 95 + 96, 95 + 97, 95 + 98, 95 + 100, 96 +97, 96 + 98, 96 + 100, 97 + 98, 97 + 100, 98 + 100, 28 + 30 + 31, 28 +30 + 32, 28 + 30 + 34, 28 + 30 + 35, 28 + 30 + 36, 28 + 30 + 55, 28 +30 + 59, 28 + 30 + 93, 28 + 30 + 94, 28 + 30 + 95, 28 + 30 + 96, 28 +30 + 97, 28 + 30 + 98, 28 + 30 + 100, 28 + 31 + 32, 28 + 31 + 34, 28 +31 + 35, 28 + 31 + 36, 28 + 31 + 55, 28 + 31 + 59, 28 + 31 + 93, 28 +31 + 94, 28 + 31 + 95, 28 + 31 + 96, 28 + 31 + 97, 28 + 31 + 98, 28 +31 + 100, 28 + 32 + 34, 28 + 32 + 35, 28 + 32 + 36, 28 + 32 + 55, 28 +32 + 59, 28 + 32 + 93, 28 + 32 + 94, 28 + 32 + 95, 28 + 32 + 96, 28 +32 + 97, 28 + 32 + 98, 28 + 32 + 100, 28 + 34 + 35, 28 + 34 + 36, 28 +34 + 55, 28 + 34 + 59, 28 + 34 + 93, 28 + 34 + 94, 28 + 34 + 95, 28 +34 + 96, 28 + 34 + 97, 28 + 34 + 98, 28 + 34 + 100, 28 + 35 + 36, 28 +35 + 55, 28 + 35 + 59, 28 + 35 + 93, 28 + 35 + 94, 28 + 35 + 95, 28 +35 + 96, 28 + 35 + 97, 28 + 35 + 98, 28 + 35 + 100, 28 + 36 + 55, 28 +36 + 59, 28 + 36 + 93, 28 + 36 + 94, 28 + 36 + 95, 28 + 36 + 96, 28 +36 + 97, 28 + 36 + 98, 28 + 36 + 100, 28 + 55 + 59, 28 + 55 + 93, 28 +55 + 94, 28 + 55 + 95, 28 + 55 + 96, 28 + 55 + 97, 28 + 55 + 98, 28 +55 + 100, 28 + 59 + 93, 28 + 59 + 94, 28 + 59 + 95, 28 + 59 + 96, 28 +59 + 97, 28 + 59 + 98, 28 + 59 + 100, 28 + 93 + 94, 28 + 93 + 95, 28 +93 + 96, 28 + 93 + 97, 28 + 93 + 98, 28 + 93 + 100, 28 + 94 + 95, 28 +94 + 96, 28 + 94 + 97, 28 + 94 + 98, 28 + 94 + 100, 28 + 95 + 96, 28 +95 + 97, 28 + 95 + 98, 28 + 95 + 100, 28 + 96 + 97, 28 + 96 + 98, 28 +96 + 100, 28 + 97 + 98, 28 + 97 + 100, 28 + 98 + 100, 30 + 31 + 32, 30 +31 + 34, 30 + 31 + 35, 30 + 31 + 36, 30 + 31 + 55, 30 + 31 + 59, 30 +31 + 93, 30 + 31 + 94, 30 + 31 + 95, 30 + 31 + 96, 30 + 31 + 97, 30 +31 + 98, 30 + 31 + 100, 30 + 32 + 34, 30 + 32 + 35, 30 + 32 + 36, 30 +32 + 55, 30 + 32 + 59, 30 + 32 + 93, 30 + 32 + 94, 30 + 32 + 95, 30 +32 + 96, 30 + 32 + 97, 30 + 32 + 98, 30 + 32 + 100, 30 + 34 + 35, 30 +34 + 36, 30 + 34 + 55, 30 + 34 + 59, 30 + 34 + 93, 30 + 34 + 94, 30 +34 + 95, 30 + 34 + 96, 30 + 34 + 97, 30 + 34 + 98, 30 + 34 + 100, 30 +35 + 36, 30 + 35 + 55, 30 + 35 + 59, 30 + 35 + 93, 30 + 35 + 94, 30 +35 + 95, 30 + 35 + 96, 30 + 35 + 97, 30 + 35 + 98, 30 + 35 + 100, 30 +36 + 55, 30 + 36 + 59, 30 + 36 + 93, 30 + 36 + 94, 30 + 36 + 95, 30 +36 + 96, 30 + 36 + 97, 30 + 36 + 98, 30 + 36 + 100, 30 + 55 + 59, 30 +55 + 93, 30 + 55 + 94, 30 + 55 + 95, 30 + 55 + 96, 30 + 55 + 97, 30 +55 + 98, 30 + 55 + 100, 30 + 59 + 93, 30 + 59 + 94, 30 + 59 + 95, 30 +59 + 96, 30 + 59 + 97, 30 + 59 + 98, 30 + 59 + 100, 30 + 93 + 94, 30 +93 + 95, 30 + 93 + 96, 30 + 93 + 97, 30 + 93 + 98, 30 + 93 + 100, 30 +94 + 95, 30 + 94 + 96, 30 + 94 + 97, 30 + 94 + 98, 30 + 94 + 100, 30 +95 + 96, 30 + 95 + 97, 30 + 95 + 98, 30 + 95 + 100, 30 + 96 + 97, 30 +96 + 98, 30 + 96 + 100, 30 + 97 + 98, 30 + 97 + 100, 30 + 98 + 100, 31 +32 + 34, 31 + 32 + 35, 31 + 32 + 36, 31 + 32 + 55, 31 + 32 + 59, 31 +32 + 93, 31 + 32 + 94, 31 + 32 + 95, 31 + 32 + 96, 31 + 32 + 97, 31 +32 + 98, 31 + 32 + 100, 31 + 34 + 35, 31 + 34 + 36, 31 + 34 + 55, 31 +34 + 59, 31 + 34 + 93, 31 + 34 + 94, 31 + 34 + 95, 31 + 34 + 96, 31 +34 + 97, 31 + 34 + 98, 31 + 34 + 100, 31 + 35 + 36, 31 + 35 + 55, 31 +35 + 59, 31 + 35 + 93, 31 + 35 + 94, 31 + 35 + 95, 31 + 35 + 96, 31 +35 + 97, 31 + 35 + 98, 31 + 35 + 100, 31 + 36 + 55, 31 + 36 + 59, 31 +36 + 93, 31 + 36 + 94, 31 + 36 + 95, 31 + 36 + 96, 31 + 36 + 97, 31 +36 + 98, 31 + 36 + 100, 31 + 55 + 59, 31 + 55 + 93, 31 + 55 + 94, 31 +55 + 95, 31 + 55 + 96, 31 + 55 + 97, 31 + 55 + 98, 31 + 55 + 100, 31 +59 + 93, 31 + 59 + 94, 31 + 59 + 95, 31 + 59 + 96, 31 + 59 + 97, 31 +59 + 98, 31 + 59 + 100, 31 + 93 + 94, 31 + 93 + 95, 31 + 93 + 96, 31 +93 + 97, 31 + 93 + 98, 31 + 93 + 100, 31 + 94 + 95, 31 + 94 + 96, 31 +94 + 97, 31 + 94 + 98, 31 + 94 + 100, 31 + 95 + 96, 31 + 95 + 97, 31 +95 + 98, 31 + 95 + 100, 31 + 96 + 97, 31 + 96 + 98, 31 + 96 + 100, 31 +97 + 98, 31 + 97 + 100, 31 + 98 + 100, 32 + 34 + 35, 32 + 34 + 36, 32 +34 + 55, 32 + 34 + 59, 32 + 34 + 93, 32 + 34 + 94, 32 + 34 + 95, 32 +34 + 96, 32 + 34 + 97, 32 + 34 + 98, 32 + 34 + 100, 32 + 35 + 36, 32 +35 + 55, 32 + 35 + 59, 32 + 35 + 93, 32 + 35 + 94, 32 + 35 + 95, 32 +35 + 96, 32 + 35 + 97, 32 + 35 + 98, 32 + 35 + 100, 32 + 36 + 55, 32 +36 + 59, 32 + 36 + 93, 32 + 36 + 94, 32 + 36 + 95, 32 + 36 + 96, 32 +36 + 97, 32 + 36 + 98, 32 + 36 + 100, 32 + 55 + 59, 32 + 55 + 93, 32 +55 + 94, 32 + 55 + 95, 32 + 55 + 96, 32 + 55 + 97, 32 + 55 + 98, 32 +55 + 100, 32 + 59 + 93, 32 + 59 + 94, 32 + 59 + 95, 32 + 59 + 96, 32 +59 + 97, 32 + 59 + 98, 32 + 59 + 100, 32 + 93 + 94, 32 + 93 + 95, 32 +93 + 96, 32 + 93 + 97, 32 + 93 + 98, 32 + 93 + 100, 32 + 94 + 95, 32 +94 + 96, 32 + 94 + 97, 32 + 94 + 98, 32 + 94 + 100, 32 + 95 + 96, 32 +95 + 97, 32 + 95 + 98, 32 + 95 + 100, 32 + 96 + 97, 32 + 96 + 98, 32 +96 + 100, 32 + 97 + 98, 32 + 97 + 100, 32 + 98 + 100, 34 + 35 + 36, 34 +35 + 55, 34 + 35 + 59, 34 + 35 + 93, 34 + 35 + 94, 34 + 35 + 95, 34 +35 + 96, 34 + 35 + 97, 34 + 35 + 98, 34 + 35 + 100, 34 + 36 + 55, 34 +36 + 59, 34 + 36 + 93, 34 + 36 + 94, 34 + 36 + 95, 34 + 36 + 96, 34 +36 + 97, 34 + 36 + 98, 34 + 36 + 100, 34 + 55 + 59, 34 + 55 + 93, 34 +55 + 94, 34 + 55 + 95, 34 + 55 + 96, 34 + 55 + 97, 34 + 55 + 98, 34 +55 + 100, 34 + 59 + 93, 34 + 59 + 94, 34 + 59 + 95, 34 + 59 + 96, 34 +59 + 97, 34 + 59 + 98, 34 + 59 + 100, 34 + 93 + 94, 34 + 93 + 95, 34 +93 + 96, 34 + 93 + 97, 34 + 93 + 98, 34 + 93 + 100, 34 + 94 + 95, 34 +94 + 96, 34 + 94 + 97, 34 + 94 + 98, 34 + 94 + 100, 34 + 95 + 96, 34 +95 + 97, 34 + 95 + 98, 34 + 95 + 100, 34 + 96 + 97, 34 + 96 + 98, 34 +96 + 100, 34 + 97 + 98, 34 + 97 + 100, 34 + 98 + 100, 35 + 36 + 55, 35 +36 + 59, 35 + 36 + 93, 35 + 36 + 94, 35 + 36 + 95, 35 + 36 + 96, 35 +36 + 97, 35 + 36 + 98, 35 + 36 + 100, 35 + 55 + 59, 35 + 55 + 93, 35 +55 + 94, 35 + 55 + 95, 35 + 55 + 96, 35 + 55 + 97, 35 + 55 + 98, 35 +55 + 100, 35 + 59 + 93, 35 + 59 + 94, 35 + 59 + 95, 35 + 59 + 96, 35 +59 + 97, 35 + 59 + 98, 35 + 59 + 100, 35 + 93 + 94, 35 + 93 + 95, 35 +93 + 96, 35 + 93 + 97, 35 + 93 + 98, 35 + 93 + 100, 35 + 94 + 95, 35 +94 + 96, 35 + 94 + 97, 35 + 94 + 98, 35 + 94 + 100, 35 + 95 + 96, 35 +95 + 97, 35 + 95 + 98, 35 + 95 + 100, 35 + 96 + 97, 35 + 96 + 98, 35 +96 + 100, 35 + 97 + 98, 35 + 97 + 100, 35 + 98 + 100, 36 + 55 + 59, 36 +55 + 93, 36 + 55 + 94, 36 + 55 + 95, 36 + 55 + 96, 36 + 55 + 97, 36 +55 + 98, 36 + 55 + 100, 36 + 59 + 93, 36 + 59 + 94, 36 + 59 + 95, 36 +59 + 96, 36 + 59 + 97, 36 + 59 + 98, 36 + 59 + 100, 36 + 93 + 94, 36 +93 + 95, 36 + 93 + 96, 36 + 93 + 97, 36 + 93 + 98, 36 + 93 + 100, 36 +94 + 95, 36 + 94 + 96, 36 + 94 + 97, 36 + 94 + 98, 36 + 94 + 100, 36 +95 + 96, 36 + 95 + 97, 36 + 95 + 98, 36 + 95 + 100, 36 + 96 + 97, 36 +96 + 98, 36 + 96 + 100, 36 + 97 + 98, 36 + 97 + 100, 36 + 98 + 100, 55 +59 + 93, 55 + 59 + 94, 55 + 59 + 95, 55 + 59 + 96, 55 + 59 + 97, 55 +59 + 98, 55 + 59 + 100, 55 + 93 + 94, 55 + 93 + 95, 55 + 93 + 96, 55 +93 + 97, 55 + 93 + 98, 55 + 93 + 100, 55 + 94 + 95, 55 + 94 + 96, 55 +94 + 97, 55 + 94 + 98, 55 + 94 + 100, 55 + 95 + 96, 55 + 95 + 97, 55 +95 + 98, 55 + 95 + 100, 55 + 96 + 97, 55 + 96 + 98, 55 + 96 + 100, 55 +97 + 98, 55 + 97 + 100, 55 + 98 + 100, 59 + 93 + 94, 59 + 93 + 95, 59 +93 + 96, 59 + 93 + 97, 59 + 93 + 98, 59 + 93 + 100, 59 + 94 + 95, 59 +94 + 96, 59 + 94 + 97, 59 + 94 + 98, 59 + 94 + 100, 59 + 95 + 96, 59 +95 + 97, 59 + 95 + 98, 59 + 95 + 100, 59 + 96 + 97, 59 + 96 + 98, 59 +96 + 100, 59 + 97 + 98, 59 + 97 + 100, 59 + 98 + 100, 93 + 94 + 95, 93 +94 + 96, 93 + 94 + 97, 93 + 94 + 98, 93 + 94 + 100, 93 + 95 + 96, 93 +95 + 97, 93 + 95 + 98, 93 + 95 + 100, 93 + 96 + 97, 93 + 96 + 98, 93 +96 + 100, 93 + 97 + 98, 93 + 97 + 100, 93 + 98 + 100, 94 + 95 + 96, 94 +95 + 97, 94 + 95 + 98, 94 + 95 + 100, 94 + 96 + 97, 94 + 96 + 98, 94 +96 + 100, 94 + 97 + 98, 94 + 97 + 100, 94 + 98 + 100, 95 + 96 + 97, 95 +96 + 98, 95 + 96 + 100, 95 + 97 + 98, 95 + 97 + 100, 95 + 98 + 100, 96 +97 + 98, 96 + 97 + 100, 96 + 98 + 100, 97 + 98 + 100,

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 1 listed in Table 1;and a light chain variable domain that that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 2, where the light chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 2 listed in Table 2.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 1, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 1 listed in Table 1,and where the heavy chain variable domain includes an alanine atposition 52 in SEQ ID NO: 1; and a light chain variable domain that thatis at least 90% (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 2, where thelight chain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 2 listedin Table 2.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 2, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 2 listed in Table 2,and where the light chain variable domain includes an alanine atposition 38 in SEQ ID NO: 2; and a heavy chain variable domain that thatis at least 90% (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, where theheavy chain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 1 listedin Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 28 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising SEQ ID NO: 2, and a heavy chain variable domain that is atleast 90% identical (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 1, where theheavy chain variable domain includes a histidine at any of the specificcombinations of one or more (e.g., two, three, four, five, six, seven,eight, nine, or ten) amino acid positions in SEQ ID NO: 1 listed inTable 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 30 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 31 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 32 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 34 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 35 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 36 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 55 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 59 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 93 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 94 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 95 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 96 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 97 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 98 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 2, wherein the light chain variabledomain includes a histidine at position 100 in SEQ ID NO: 2; and a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 1, where the heavy chain variable domain includes a histidine atany of the specific combinations of one or more amino acid positions inSEQ ID NO: 1 listed in Table 1.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain ofmirvetuximab with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) histidine(s)substituted with an alanine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of mirvetuximab with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) histidine(s) substituted with an alanine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of mirvetuximab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) histidines substituted with an alanine;and a light chain variable domain of mirvetuximab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) histidine(s) substituted with an alanine.In some examples of any of the ABPCs described herein, the heavy chainvariable domain of mirvetuximab comprises SEQ ID NO: 1. In some examplesof any of the ABPCs described herein, the light chain variable domain ofmirvetuximab comprises SEQ ID NO: 2.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 3, SEQ ID NO: 4, andSEQ ID NO: 5, respectively, with collectively a total of one or more(e.g., one, two, three, four, five, six, seven, eight, nine, or ten)histidine(s) in SEQ ID NOs: 3-5 substituted with an alanine. In someexamples of any of the ABPCs described herein, the first antigen-bindingdomain comprises a light chain variable domain comprising a CDR1, aCDR2, and a CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8,respectively, with collectively a total of one or more (e.g., one, two,three, four, five, six, seven, eight, nine, or ten) histidine(s) in SEQID NOs: 6-8 substituted with an alanine. In some examples of any of theABPCs described herein, the first antigen-binding domain includes: aheavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, respectively, withcollectively a total of one or more (e.g., one, two, three, four, five,six, seven, eight, nine, or ten) histidine(s) in SEQ ID NOs: 3-5substituted with an alanine; and a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 6, SEQ ID NO: 7, andSEQ ID NO: 8, respectively, with collectively a total of one or more(e.g., one, two, three, four, five, six, seven, eight, nine, or ten)histidine(s) in SEQ ID NOs: 6-8 substituted with an alanine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21,SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO:26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ IDNO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40,SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO:45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ IDNO: 50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain of SEQ IDNO: 2, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62,SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO:67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ IDNO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81,SEQ ID NO: 82, SEQ ID NO: 83, or SEQ ID NO: 84.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 2, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 54, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 55, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 56, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 57, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 58, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 59, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 60, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 61, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 62, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 63, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 64, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 65, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 66, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 67, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 68, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 69, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 70, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 71, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 72, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 73, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 74, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 75, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 76, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 77, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 78, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 79, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 80, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 81, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 82, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 83, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 84, and a heavy chain variable domain comprising: SEQ ID NO:1, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ IDNO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26,SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO:31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ IDNO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45,SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO:50, SEQ ID NO: 51, SEQ ID NO: 52, or SEQ ID NO: 53.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO:89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ IDNO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, or SEQ ID NO: 104.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO:62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ IDNO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 85, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 86, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 87, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 88, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 89, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 90, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 91, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 92, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 93, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 94, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 95, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 96, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 97, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 98, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 99, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domaincomprising: SEQ ID NO: 100, and a light chain variable domain comprisingSEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO:62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ IDNO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 101, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 102, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 103, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain comprisingSEQ ID NO: 104, and a light chain variable domain comprising: SEQ ID NO:2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ IDNO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain ofSTRO-002 with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) amino acidssubstituted with a histidine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of STRO-002 with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acids substituted with a histidine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of STRO-002 with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acids substituted with a histidine;and a light chain variable domain of STRO-002 with one or more (e.g.,one, two, three, four, five, six, seven, eight, nine, ten, eleven,twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen,nineteen, or twenty) amino acids substituted with a histidine. In someexamples of any of the ABPCs described herein, the heavy chain variabledomain of STRO-002 comprises SEQ ID NO: 105. In some examples of any ofthe ABPCs described herein, the light chain variable domain of STRO-002comprises SEQ ID NO: 106.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 107, SEQ ID NO: 108,and SEQ ID NO: 109, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 107-109 substituted with ahistidine. In some examples of any of the ABPCs described herein, thefirst antigen-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 110, SEQ ID NO: 111,and SEQ ID NO: 112, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 110-112 substituted with ahistidine. In some examples of any of the ABPCs described herein, thefirst antigen-binding domain includes: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 107, SEQ ID NO: 108,and SEQ ID NO: 109, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 107-109 substituted with ahistidine; and a light chain variable domain comprising a CDR1, a CDR2,and a CDR3 of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112,respectively, with collectively a total of one or more (e.g., one, two,three, four, five, six, seven, eight, nine, or ten) amino acid positionsin SEQ ID NOs: 110-112 substituted with a histidine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 105 selected from the groupconsisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103,108, 109, 110, 111, 112, and 113. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 106, where the light chain variable domain includes a histidineat one or more (e.g., one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 106 selected from the group consisting of: 28, 29, 30, 31, 50, 92,93, 94, 95, and 96. In some examples of any of the ABPCs describedherein the first antigen-binding domain includes: a heavy chain variabledomain that is at least 90% (e.g., at least 92%, at least 94%, at least96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 105,where the heavy chain variable domain includes a histidine at one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acid positions in SEQ ID NO: 105selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55,56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113, and a lightchain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 106, where the light chain variable domain includes a histidineat one or more (e.g., one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 106 selected from the group consisting of: 28, 29, 30, 31, 50, 92,93, 94, 95, and 96.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 105, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes an alanine at position 35 in SEQ ID NO:105.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a heavy chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes an alanine at position 35 in SEQ ID NO:105, and a light chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 106, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 106 selected from the group consisting of: 28,29, 30, 31, 50, 92, 93, 94, 95, and 96.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 105 selected from the groupconsisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103,108, 109, 110, 111, 112, and 113, and where the heavy chain variabledomain includes an alanine at position 35 in SEQ ID NO: 105. In someexamples of any of the ABPCs described herein the first antigen-bindingdomain includes: a heavy chain variable domain that is at least 90%(e.g., at least 92%, at least 94%, at least 96%, at least 98%, at least99%, or 100%) identical to SEQ ID NO: 105, where the heavy chainvariable domain includes a histidine at one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 105 selected from the groupconsisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103,108, 109, 110, 111, 112, and 113, and where the heavy chain variabledomain includes an alanine at position 35 in SEQ ID NO: 105, and a lightchain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 106, where the light chain variable domain includes a histidineat one or more (e.g., one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 106 selected from the group consisting of: 28, 29, 30, 31, 50, 92,93, 94, 95, and 96.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 105, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 105 listed in Table 3and where the heavy chain variable domain includes an alanine atposition 35 of SEQ ID NO: 105.

TABLE 3 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 105that can be Substituted with Histidine 29 + 33, 29 + 34, 29 + 50, 29 +51, 29 + 52, 29 + 53, 29 + 55, 29 + 56, 29 + 57, 29 + 101, 29 + 102,29 + 103, 29 + 108, 29 + 109, 29 + 110, 29 + 111, 29 + 112, 29 + 113,33 + 34, 33 + 50, 33 + 51, 33 + 52, 33 + 53, 33 + 55, 33 + 56, 33 + 57,33 + 101, 33 + 102, 33 + 103, 33 + 108, 33 + 109, 33 + 110, 33 + 111,33 + 112, 33 + 113, 34 + 50, 34 + 51, 34 + 52, 34 + 53, 34 + 55, 34 +56, 34 + 57, 34 + 101, 34 + 102, 34 + 103, 34 + 108, 34 + 109, 34 + 110,34 + 111, 34 + 112, 34 + 113, 50 + 51, 50 + 52, 50 + 53, 50 + 55, 50 +56, 50 + 57, 50 + 101, 50 + 102, 50 + 103, 50 + 108, 50 + 109, 50 + 110,50 + 111, 50 + 112, 50 + 113, 51 + 52, 51 + 53, 51 + 55, 51 + 56, 51 +57, 51 + 101, 51 + 102, 51 + 103, 51 + 108, 51 + 109, 51 + 110, 51 +111, 51 + 112, 51 + 113, 52 + 53, 52 + 55, 52 + 56, 52 + 57, 52 + 101,52 + 102, 52 + 103, 52 + 108, 52 + 109, 52 + 110, 52 + 111, 52 + 112,52 + 113, 53 + 55, 53 + 56, 53 + 57, 53 + 101, 53 + 102, 53 + 103, 53 +108, 53 + 109, 53 + 110, 53 + 111, 53 + 112, 53 + 113, 55 + 56, 55 + 57,55 + 101, 55 + 102, 55 + 103, 55 + 108, 55 + 109, 55 + 110, 55 + 111,55 + 112, 55 + 113, 56 + 57, 56 + 101, 56 + 102, 56 + 103, 56 + 108,56 + 109, 56 + 110, 56 + 111, 56 + 112, 56 + 113, 57 + 101, 57 + 102,57 + 103, 57 + 108, 57 + 109, 57 + 110, 57 + 111, 57 + 112, 57 + 113,101 + 102, 101 + 103, 101 + 108, 101 + 109, 101 + 110, 101 + 111, 101 +112, 101 + 113, 102 + 103, 102 + 108, 102 + 109, 102 + 110, 102 + 111,102 + 112, 102 + 113, 103 + 108, 103 + 109, 103 + 110, 103 + 111, 103 +112, 103 + 113, 108 + 109, 108 + 110, 108 + 111, 108 + 112, 108 + 113,109 + 110, 109 + 111, 109 + 112, 109 + 113, 110 + 111, 110 + 112, 110 +113, 111 + 112, 111 + 113, 112 + 113, 29 + 33 + 34, 29 + 33 + 50, 29 +33 + 51, 29 + 33 + 52, 29 + 33 + 53, 29 + 33 + 55, 29 + 33 + 56, 29 +33 + 57, 29 + 33 + 101, 29 + 33 + 102, 29 + 33 + 103, 29 + 33 + 108,29 + 33 + 109, 29 + 33 + 110, 29 + 33 + 111, 29 + 33 + 112, 29 + 33 +113, 29 + 34 + 50, 29 + 34 + 51, 29 + 34 + 52, 29 + 34 + 53, 29 + 34 +55, 29 + 34 + 56, 29 + 34 + 57, 29 + 34 + 101, 29 + 34 + 102, 29 + 34 +103, 29 + 34 + 108, 29 + 34 + 109, 29 + 34 + 110, 29 + 34 + 111, 29 +34 + 112, 29 + 34 + 113, 29 + 50 + 51, 29 + 50 + 52, 29 + 50 + 53, 29 +50 + 55, 29 + 50 + 56, 29 + 50 + 57, 29 + 50 + 101, 29 + 50 + 102, 29 +50 + 103, 29 + 50 + 108, 29 + 50 + 109, 29 + 50 + 110, 29 + 50 + 111,29 + 50 + 112, 29 + 50 + 113, 29 + 51 + 52, 29 + 51 + 53, 29 + 51 + 55,29 + 51 + 56, 29 + 51 + 57, 29 + 51 + 101, 29 + 51 + 102, 29 + 51 + 103,29 + 51 + 108, 29 + 51 + 109, 29 + 51 + 110, 29 + 51 + 111, 29 + 51 +112, 29 + 51 + 113, 29 + 52 + 53, 29 + 52 + 55, 29 + 52 + 56, 29 + 52 +57, 29 + 52 + 101, 29 + 52 + 102, 29 + 52 + 103, 29 + 52 + 108, 29 +52 + 109, 29 + 52 + 110, 29 + 52 + 111, 29 + 52 + 112, 29 + 52 + 113,29 + 53 + 55, 29 + 53 + 56, 29 + 53 + 57, 29 + 53 + 101, 29 + 53 + 102,29 + 53 + 103, 29 + 53 + 108, 29 + 53 + 109, 29 + 53 + 110, 29 + 53 +111, 29 + 53 + 112, 29 + 53 + 113, 29 + 55 + 56, 29 + 55 + 57, 29 + 55 +101, 29 + 55 + 102, 29 + 55 + 103, 29 + 55 + 108, 29 + 55 + 109, 29 +55 + 110, 29 + 55 + 111, 29 + 55 + 112, 29 + 55 + 113, 29 + 56 + 57,29 + 56 + 101, 29 + 56 + 102, 29 + 56 + 103, 29 + 56 + 108, 29 + 56 +109, 29 + 56 + 110, 29 + 56 + 111, 29 + 56 + 112, 29 + 56 + 113, 29 +57 + 101, 29 + 57 + 102, 29 + 57 + 103, 29 + 57 + 108, 29 + 57 + 109,29 + 57 + 110, 29 + 57 + 111, 29 + 57 + 112, 29 + 57 + 113, 29 + 101 +102, 29 + 101 + 103, 29 + 101 + 108, 29 + 101 + 109, 29 + 101 + 110,29 + 101 + 111, 29 + 101 + 112, 29 + 101 + 113, 29 + 102 + 103, 29 +102 + 108, 29 + 102 + 109, 29 + 102 + 110, 29 + 102 + 111, 29 + 102 +112, 29 + 102 + 113, 29 + 103 + 108, 29 + 103 + 109, 29 + 103 + 110,29 + 103 + 111, 29 + 103 + 112, 29 + 103 + 113, 29 + 108 + 109, 29 +108 + 110, 29 + 108 + 111, 29 + 108 + 112, 29 + 108 + 113, 29 + 109 +110, 29 + 109 + 111, 29 + 109 + 112, 29 + 109 + 113, 29 + 110 + 111,29 + 110 + 112, 29 + 110 + 113, 29 + 111 + 112, 29 + 111 + 113, 29 +112 + 113, 33 + 34 + 50, 33 + 34 + 51, 33 + 34 + 52, 33 + 34 + 53, 33 +34 + 55, 33 + 34 + 56, 33 + 34 + 57, 33 + 34 + 101, 33 + 34 + 102, 33 +34 + 103, 33 + 34 + 108, 33 + 34 + 109, 33 + 34 + 110, 33 + 34 + 111,33 + 34 + 112, 33 + 34 + 113, 33 + 50 + 51, 33 + 50 + 52, 33 + 50 + 53,33 + 50 + 55, 33 + 50 + 56, 33 + 50 + 57, 33 + 50 + 101, 33 + 50 + 102,33 + 50 + 103, 33 + 50 + 108, 33 + 50 + 109, 33 + 50 + 110, 33 + 50 +111, 33 + 50 + 112, 33 + 50 + 113, 33 + 51 + 52, 33 + 51 + 53, 33 + 51 +55, 33 + 51 + 56, 33 + 51 + 57, 33 + 51 + 101, 33 + 51 + 102, 33 + 51 +103, 33 + 51 + 108, 33 + 51 + 109, 33 + 51 + 110, 33 + 51 + 111, 33 +51 + 112, 33 + 51 + 113, 33 + 52 + 53, 33 + 52 + 55, 33 + 52 + 56, 33 +52 + 57, 33 + 52 + 101, 33 + 52 + 102, 33 + 52 + 103, 33 + 52 + 108,33 + 52 + 109, 33 + 52 + 110, 33 + 52 + 111, 33 + 52 + 112, 33 + 52 +113, 33 + 53 + 55, 33 + 53 + 56, 33 + 53 + 57, 33 + 53 + 101, 33 + 53 +102, 33 + 53 + 103, 33 + 53 + 108, 33 + 53 + 109, 33 + 53 + 110, 33 +53 + 111, 33 + 53 + 112, 33 + 53 + 113, 33 + 55 + 56, 33 + 55 + 57, 33 +55 + 101, 33 + 55 + 102, 33 + 55 + 103, 33 + 55 + 108, 33 + 55 + 109,33 + 55 + 110, 33 + 55 + 111, 33 + 55 + 112, 33 + 55 + 113, 33 + 56 +57, 33 + 56 + 101, 33 + 56 + 102, 33 + 56 + 103, 33 + 56 + 108, 33 +56 + 109, 33 + 56 + 110, 33 + 56 + 111, 33 + 56 + 112, 33 + 56 + 113,33 + 57 + 101, 33 + 57 + 102, 33 + 57 + 103, 33 + 57 + 108, 33 + 57 +109, 33 + 57 + 110, 33 + 57 + 111, 33 + 57 + 112, 33 + 57 + 113, 33 +101 + 102, 33 + 101 + 103, 33 + 101 + 108, 33 + 101 + 109, 33 + 101 +110, 33 + 101 + 111, 33 + 101 + 112, 33 + 101 + 113, 33 + 102 + 103,33 + 102 + 108, 33 + 102 + 109, 33 + 102 + 110, 33 + 102 + 111, 33 +102 + 112, 33 + 102 + 113, 33 + 103 + 108, 33 + 103 + 109, 33 + 103 +110, 33 + 103 + 111, 33 + 103 + 112, 33 + 103 + 113, 33 + 108 + 109,33 + 108 + 110, 33 + 108 + 111, 33 + 108 + 112, 33 + 108 + 113, 33 +109 + 110, 33 + 109 + 111, 33 + 109 + 112, 33 + 109 + 113, 33 + 110 +111, 33 + 110 + 112, 33 + 110 + 113, 33 + 111 + 112, 33 + 111 + 113,33 + 112 + 113, 34 + 50 + 51, 34 + 50 + 52, 34 + 50 + 53, 34 + 50 + 55,34 + 50 + 56, 34 + 50 + 57, 34 + 50 + 101, 34 + 50 + 102, 34 + 50 + 103,34 + 50 + 108, 34 + 50 + 109, 34 + 50 + 110, 34 + 50 + 111, 34 + 50 +112, 34 + 50 + 113, 34 + 51 + 52, 34 + 51 + 53, 34 + 51 + 55, 34 + 51 +56, 34 + 51 + 57, 34 + 51 + 101, 34 + 51 + 102, 34 + 51 + 103, 34 + 51 +108, 34 + 51 + 109, 34 + 51 + 110, 34 + 51 + 111, 34 + 51 + 112, 34 +51 + 113, 34 + 52 + 53, 34 + 52 + 55, 34 + 52 + 56, 34 + 52 + 57, 34 +52 + 101, 34 + 52 + 102, 34 + 52 + 103, 34 + 52 + 108, 34 + 52 + 109,34 + 52 + 110, 34 + 52 + 111, 34 + 52 + 112, 34 + 52 + 113, 34 + 53 +55, 34 + 53 + 56, 34 + 53 + 57, 34 + 53 + 101, 34 + 53 + 102, 34 + 53 +103, 34 + 53 + 108, 34 + 53 + 109, 34 + 53 + 110, 34 + 53 + 111, 34 +53 + 112, 34 + 53 + 113, 34 + 55 + 56, 34 + 55 + 57, 34 + 55 + 101, 34 +55 + 102, 34 + 55 + 103, 34 + 55 + 108, 34 + 55 + 109, 34 + 55 + 110,34 + 55 + 111, 34 + 55 + 112, 34 + 55 + 113, 34 + 56 + 57, 34 + 56 +101, 34 + 56 + 102, 34 + 56 + 103, 34 + 56 + 108, 34 + 56 + 109, 34 +56 + 110, 34 + 56 + 111, 34 + 56 + 112, 34 + 56 + 113, 34 + 57 + 101,34 + 57 + 102, 34 + 57 + 103, 34 + 57 + 108, 34 + 57 + 109, 34 + 57 +110, 34 + 57 + 111, 34 + 57 + 112, 34 + 57 + 113, 34 + 101 + 102, 34 +101 + 103, 34 + 101 + 108, 34 + 101 + 109, 34 + 101 + 110, 34 + 101 +111, 34 + 101 + 112, 34 + 101 + 113, 34 + 102 + 103, 34 + 102 + 108,34 + 102 + 109, 34 + 102 + 110, 34 + 102 + 111, 34 + 102 + 112, 34 +102 + 113, 34 + 103 + 108, 34 + 103 + 109, 34 + 103 + 110, 34 + 103 +111, 34 + 103 + 112, 34 + 103 + 113, 34 + 108 + 109, 34 + 108 + 110,34 + 108 + 111, 34 + 108 + 112, 34 + 108 + 113, 34 + 109 + 110, 34 +109 + 111, 34 + 109 + 112, 34 + 109 + 113, 34 + 110 + 111, 34 + 110 +112, 34 + 110 + 113, 34 + 111 + 112, 34 + 111 + 113, 34 + 112 + 113,50 + 51 + 52, 50 + 51 + 53, 50 + 51 + 55, 50 + 51 + 56, 50 + 51 + 57,50 + 51 + 101, 50 + 51 + 102, 50 + 51 + 103, 50 + 51 + 108, 50 + 51 +109, 50 + 51 + 110, 50 + 51 + 111, 50 + 51 + 112, 50 + 51 + 113, 50 +52 + 53, 50 + 52 + 55, 50 + 52 + 56, 50 + 52 + 57, 50 + 52 + 101, 50 +52 + 102, 50 + 52 + 103, 50 + 52 + 108, 50 + 52 + 109, 50 + 52 + 110,50 + 52 + 111, 50 + 52 + 112, 50 + 52 + 113, 50 + 53 + 55, 50 + 53 + 56,50 + 53 + 57, 50 + 53 + 101, 50 + 53 + 102, 50 + 53 + 103, 50 + 53 +108, 50 + 53 + 109, 50 + 53 + 110, 50 + 53 + 111, 50 + 53 + 112, 50 +53 + 113, 50 + 55 + 56, 50 + 55 + 57, 50 + 55 + 101, 50 + 55 + 102, 50 +55 + 103, 50 + 55 + 108, 50 + 55 + 109, 50 + 55 + 110, 50 + 55 + 111,50 + 55 + 112, 50 + 55 + 113, 50 + 56 + 57, 50 + 56 + 101, 50 + 56 +102, 50 + 56 + 103, 50 + 56 + 108, 50 + 56 + 109, 50 + 56 + 110, 50 +56 + 111, 50 + 56 + 112, 50 + 56 + 113, 50 + 57 + 101, 50 + 57 + 102,50 + 57 + 103, 50 + 57 + 108, 50 + 57 + 109, 50 + 57 + 110, 50 + 57 +111, 50 + 57 + 112, 50 + 57 + 113, 50 + 101 + 102, 50 + 101 + 103, 50 +101 + 108, 50 + 101 + 109, 50 + 101 + 110, 50 + 101 + 111, 50 + 101 +112, 50 + 101 + 113, 50 + 102 + 103, 50 + 102 + 108, 50 + 102 + 109,50 + 102 + 110, 50 + 102 + 111, 50 + 102 + 112, 50 + 102 + 113, 50 +103 + 108, 50 + 103 + 109, 50 + 103 + 110, 50 + 103 + 111, 50 + 103 +112, 50 + 103 + 113, 50 + 108 + 109, 50 + 108 + 110, 50 + 108 + 111,50 + 108 + 112, 50 + 108 + 113, 50 + 109 + 110, 50 + 109 + 111, 50 +109 + 112, 50 + 109 + 113, 50 + 110 + 111, 50 + 110 + 112, 50 + 110 +113, 50 + 111 + 112, 50 + 111 + 113, 50 + 112 + 113, 51 + 52 + 53, 51 +52 + 55, 51 + 52 + 56, 51 + 52 + 57, 51 + 52 + 101, 51 + 52 + 102, 51 +52 + 103, 51 + 52 + 108, 51 + 52 + 109, 51 + 52 + 110, 51 + 52 + 111,51 + 52 + 112, 51 + 52 + 113, 51 + 53 + 55, 51 + 53 + 56, 51 + 53 + 57,51 + 53 + 101, 51 + 53 + 102, 51 + 53 + 103, 51 + 53 + 108, 51 + 53 +109, 51 + 53 + 110, 51 + 53 + 111, 51 + 53 + 112, 51 + 53 + 113, 51 +55 + 56, 51 + 55 + 57, 51 + 55 + 101, 51 + 55 + 102, 51 + 55 + 103, 51 +55 + 108, 51 + 55 + 109, 51 + 55 + 110, 51 + 55 + 111, 51 + 55 + 112,51 + 55 + 113, 51 + 56 + 57, 51 + 56 + 101, 51 + 56 + 102, 51 + 56 +103, 51 + 56 + 108, 51 + 56 + 109, 51 + 56 + 110, 51 + 56 + 111, 51 +56 + 112, 51 + 56 + 113, 51 + 57 + 101, 51 + 57 + 102, 51 + 57 + 103,51 + 57 + 108, 51 + 57 + 109, 51 + 57 + 110, 51 + 57 + 111, 51 + 57 +112, 51 + 57 + 113, 51 + 101 + 102, 51 + 101 + 103, 51 + 101 + 108, 51 +101 + 109, 51 + 101 + 110, 51 + 101 + 111, 51 + 101 + 112, 51 + 101 +113, 51 + 102 + 103, 51 + 102 + 108, 51 + 102 + 109, 51 + 102 + 110,51 + 102 + 111, 51 + 102 + 112, 51 + 102 + 113, 51 + 103 + 108, 51 +103 + 109, 51 + 103 + 110, 51 + 103 + 111, 51 + 103 + 112, 51 + 103 +113, 51 + 108 + 109, 51 + 108 + 110, 51 + 108 + 111, 51 + 108 + 112,51 + 108 + 113, 51 + 109 + 110, 51 + 109 + 111, 51 + 109 + 112, 51 +109 + 113, 51 + 110 + 111, 51 + 110 + 112, 51 + 110 + 113, 51 + 111 +112, 51 + 111 + 113, 51 + 112 + 113, 52 + 53 + 55, 52 + 53 + 56, 52 +53 + 57, 52 + 53 + 101, 52 + 53 + 102, 52 + 53 + 103, 52 + 53 + 108,52 + 53 + 109, 52 + 53 + 110, 52 + 53 + 111, 52 + 53 + 112, 52 + 53 +113, 52 + 55 + 56, 52 + 55 + 57, 52 + 55 + 101, 52 + 55 + 102, 52 + 55 +103, 52 + 55 + 108, 52 + 55 + 109, 52 + 55 + 110, 52 + 55 + 111, 52 +55 + 112, 52 + 55 + 113, 52 + 56 + 57, 52 + 56 + 101, 52 + 56 + 102,52 + 56 + 103, 52 + 56 + 108, 52 + 56 + 109, 52 + 56 + 110, 52 + 56 +111, 52 + 56 + 112, 52 + 56 + 113, 52 + 57 + 101, 52 + 57 + 102, 52 +57 + 103, 52 + 57 + 108, 52 + 57 + 109, 52 + 57 + 110, 52 + 57 + 111,52 + 57 + 112, 52 + 57 + 113, 52 + 101 + 102, 52 + 101 + 103, 52 + 101 +108, 52 + 101 + 109, 52 + 101 + 110, 52 + 101 + 111, 52 + 101 + 112,52 + 101 + 113, 52 + 102 + 103, 52 + 102 + 108, 52 + 102 + 109, 52 +102 + 110, 52 + 102 + 111, 52 + 102 + 112, 52 + 102 + 113, 52 + 103 +108, 52 + 103 + 109, 52 + 103 + 110, 52 + 103 + 111, 52 + 103 + 112,52 + 103 + 113, 52 + 108 + 109, 52 + 108 + 110, 52 + 108 + 111, 52 +108 + 112, 52 + 108 + 113, 52 + 109 + 110, 52 + 109 + 111, 52 + 109 +112, 52 + 109 + 113, 52 + 110 + 111, 52 + 110 + 112, 52 + 110 + 113,52 + 111 + 112, 52 + 111 + 113, 52 + 112 + 113, 53 + 55 + 56, 53 + 55 +57, 53 + 55 + 101, 53 + 55 + 102, 53 + 55 + 103, 53 + 55 + 108, 53 +55 + 109, 53 + 55 + 110, 53 + 55 + 111, 53 + 55 + 112, 53 + 55 + 113,53 + 56 + 57, 53 + 56 + 101, 53 + 56 + 102, 53 + 56 + 103, 53 + 56 +108, 53 + 56 + 109, 53 + 56 + 110, 53 + 56 + 111, 53 + 56 + 112, 53 +56 + 113, 53 + 57 + 101, 53 + 57 + 102, 53 + 57 + 103, 53 + 57 + 108,53 + 57 + 109, 53 + 57 + 110, 53 + 57 + 111, 53 + 57 + 112, 53 + 57 +113, 53 + 101 + 102, 53 + 101 + 103, 53 + 101 + 108, 53 + 101 + 109,53 + 101 + 110, 53 + 101 + 111, 53 + 101 + 112, 53 + 101 + 113, 53 +102 + 103, 53 + 102 + 108, 53 + 102 + 109, 53 + 102 + 110, 53 + 102 +111, 53 + 102 + 112, 53 + 102 + 113, 53 + 103 + 108, 53 + 103 + 109,53 + 103 + 110, 53 + 103 + 111, 53 + 103 + 112, 53 + 103 + 113, 53 +108 + 109, 53 + 108 + 110, 53 + 108 + 111, 53 + 108 + 112, 53 + 108 +113, 53 + 109 + 110, 53 + 109 + 111, 53 + 109 + 112, 53 + 109 + 113,53 + 110 + 111, 53 + 110 + 112, 53 + 110 + 113, 53 + 111 + 112, 53 +111 + 113, 53 + 112 + 113, 55 + 56 + 57, 55 + 56 + 101, 55 + 56 + 102,55 + 56 + 103, 55 + 56 + 108, 55 + 56 + 109, 55 + 56 + 110, 55 + 56 +111, 55 + 56 + 112, 55 + 56 + 113, 55 + 57 + 101, 55 + 57 + 102, 55 +57 + 103, 55 + 57 + 108, 55 + 57 + 109, 55 + 57 + 110, 55 + 57 + 111,55 + 57 + 112, 55 + 57 + 113, 55 + 101 + 102, 55 + 101 + 103, 55 + 101 +108, 55 + 101 + 109, 55 + 101 + 110, 55 + 101 + 111, 55 + 101 + 112,55 + 101 + 113, 55 + 102 + 103, 55 + 102 + 108, 55 + 102 + 109, 55 +102 + 110, 55 + 102 + 111, 55 + 102 + 112, 55 + 102 + 113, 55 + 103 +108, 55 + 103 + 109, 55 + 103 + 110, 55 + 103 + 111, 55 + 103 + 112,55 + 103 + 113, 55 + 108 + 109, 55 + 108 + 110, 55 + 108 + 111, 55 +108 + 112, 55 + 108 + 113, 55 + 109 + 110, 55 + 109 + 111, 55 + 109 +112, 55 + 109 + 113, 55 + 110 + 111, 55 + 110 + 112, 55 + 110 + 113,55 + 111 + 112, 55 + 111 + 113, 55 + 112 + 113, 56 + 57 + 101, 56 + 57 +102, 56 + 57 + 103, 56 + 57 + 108, 56 + 57 + 109, 56 + 57 + 110, 56 +57 + 111, 56 + 57 + 112, 56 + 57 + 113, 56 + 101 + 102, 56 + 101 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57 + 109 + 113, 57 + 110 + 111,57 + 110 + 112, 57 + 110 + 113, 57 + 111 + 112, 57 + 111 + 113, 57 +112 + 113, 101 + 102 + 103, 101 + 102 + 108, 101 + 102 + 109, 101 +102 + 110, 101 + 102 + 111, 101 + 102 + 112, 101 + 102 + 113, 101 +103 + 108, 101 + 103 + 109, 101 + 103 + 110, 101 + 103 + 111, 101 +103 + 112, 101 + 103 + 113, 101 + 108 + 109, 101 + 108 + 110, 101 +108 + 111, 101 + 108 + 112, 101 + 108 + 113, 101 + 109 + 110, 101 +109 + 111, 101 + 109 + 112, 101 + 109 + 113, 101 + 110 + 111, 101 +110 + 112, 101 + 110 + 113, 101 + 111 + 112, 101 + 111 + 113, 101 +112 + 113, 102 + 103 + 108, 102 + 103 + 109, 102 + 103 + 110, 102 +103 + 111, 102 + 103 + 112, 102 + 103 + 113, 102 + 108 + 109, 102 +108 + 110, 102 + 108 + 111, 102 + 108 + 112, 102 + 108 + 113, 102 +109 + 110, 102 + 109 + 111, 102 + 109 + 112, 102 + 109 + 113, 102 +110 + 111, 102 + 110 + 112, 102 + 110 + 113, 102 + 111 + 112, 102 +111 + 113, 102 + 112 + 113, 103 + 108 + 109, 103 + 108 + 110, 103 +108 + 111, 103 + 108 + 112, 103 + 108 + 113, 103 + 109 + 110, 103 +109 + 111, 103 + 109 + 112, 103 + 109 + 113, 103 + 110 + 111, 103 +110 + 112, 103 + 110 + 113, 103 + 111 + 112, 103 + 111 + 113, 103 +112 + 113, 108 + 109 + 110, 108 + 109 + 111, 108 + 109 + 112, 108 +109 + 113, 108 + 110 + 111, 108 + 110 + 112, 108 + 110 + 113, 108 +111 + 112, 108 + 111 + 113, 108 + 112 + 113, 109 + 110 + 111, 109 +110 + 112, 109 + 110 + 113, 109 + 111 + 112, 109 + 111 + 113, 109 +112 + 113, 110 + 111 + 112, 110 + 111 + 113, 110 + 112 + 113, 111 +112 + 113

In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 106, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 106 listed in Table 4.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes an alanine at position 91 in SEQ ID NO:106.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a light chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes an alanine at position 91 in SEQ ID NO:2, and a heavy chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 105 selected from the group consisting of: 29,33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111,112, and 113.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 106 selected from the groupconsisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96, and where thelight chain variable domain includes an alanine at position 91 in SEQ IDNO: 106. In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a light chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 106 selected from the groupconsisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96, and where thelight chain variable domain includes an alanine at position 91 in SEQ IDNO: 106, and a heavy chain variable domain that is at least 90% (e.g.,at least 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 105 selected from the group consisting of: 29,33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111,112, and 113.

In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 106, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 106 listed in Table 4and where the light chain variable domain includes an alanine atposition 91 of SEQ ID NO: 106.

TABLE 4 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 106that can be Substituted with Histidine 28 + 29, 28 + 30, 28 + 31, 28 +50, 28 + 92, 28 + 93, 28 + 94, 28 + 95, 28 + 96, 29 + 30, 29 + 31, 29 +50, 29 + 92, 29 + 93, 29 + 94, 29 + 95, 29 + 96, 30 + 31, 30 + 50, 30 +92, 30 + 93, 30 + 94, 30 + 95, 30 + 96, 31 + 50, 31 + 92, 31 + 93, 31 +94, 31 + 95, 31 + 96, 50 + 92, 50 + 93, 50 + 94, 50 + 95, 50 + 96, 92 +93, 92 + 94, 92 + 95, 92 + 96, 93 + 94, 93 + 95, 93 + 96, 94 + 95, 94 +96, 95 + 96, 28 + 29 + 30, 28 + 29 + 31, 28 + 29 + 50, 28 + 29 + 92,28 + 29 + 93, 28 + 29 + 94, 28 + 29 + 95, 28 + 29 + 96, 28 + 30 + 31,28 + 30 + 50, 28 + 30 + 92, 28 + 30 + 93, 28 + 30 + 94, 28 + 30 + 95,28 + 30 + 96, 28 + 31 + 50, 28 + 31 + 92, 28 + 31 + 93, 28 + 31 + 94,28 + 31 + 95, 28 + 31 + 96, 28 + 50 + 92, 28 + 50 + 93, 28 + 50 + 94,28 + 50 + 95, 28 + 50 + 96, 28 + 92 + 93, 28 + 92 + 94, 28 + 92 + 95,28 + 92 + 96, 28 + 93 + 94, 28 + 93 + 95, 28 + 93 + 96, 28 + 94 + 95,28 + 94 + 96, 28 + 95 + 96, 29 + 30 + 31, 29 + 30 + 50, 29 + 30 + 92,29 + 30 + 93, 29 + 30 + 94, 29 + 30 + 95, 29 + 30 + 96, 29 + 31 + 50,29 + 31 + 92, 29 + 31 + 93, 29 + 31 + 94, 29 + 31 + 95, 29 + 31 + 96,29 + 50 + 92, 29 + 50 + 93, 29 + 50 + 94, 29 + 50 + 95, 29 + 50 + 96,29 + 92 + 93, 29 + 92 + 94, 29 + 92 + 95, 29 + 92 + 96, 29 + 93 + 94,29 + 93 + 95, 29 + 93 + 96, 29 + 94 + 95, 29 + 94 + 96, 29 + 95 + 96,30 + 31 + 50, 30 + 31 + 92, 30 + 31 + 93, 30 + 31 + 94, 30 + 31 + 95,30 + 31 + 96, 30 + 50 + 92, 30 + 50 + 93, 30 + 50 + 94, 30 + 50 + 95,30 + 50 + 96, 30 + 92 + 93, 30 + 92 + 94, 30 + 92 + 95, 30 + 92 + 96,30 + 93 + 94, 30 + 93 + 95, 30 + 93 + 96, 30 + 94 + 95, 30 + 94 + 96,30 + 95 + 96, 31 + 50 + 92, 31 + 50 + 93, 31 + 50 + 94, 31 + 50 + 95,31 + 50 + 96, 31 + 92 + 93, 31 + 92 + 94, 31 + 92 + 95, 31 + 92 + 96,31 + 93 + 94, 31 + 93 + 95, 31 + 93 + 96, 31 + 94 + 95, 31 + 94 + 96,31 + 95 + 96, 50 + 92 + 93, 50 + 92 + 94, 50 + 92 + 95, 50 + 92 + 96,50 + 93 + 94, 50 + 93 + 95, 50 + 93 + 96, 50 + 94 + 95, 50 + 94 + 96,50 + 95 + 96, 92 + 93 + 94, 92 + 93 + 95, 92 + 93 + 96, 92 + 94 + 95,92 + 94 + 96, 92 + 95 + 96, 93 + 94 + 95, 93 + 94 + 96, 93 + 95 + 96,94 + 95 + 96,

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 105listed in Table 3; and a light chain variable domain that that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 106listed in Table 4.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 105, where the heavychain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 105listed in Table 3, and where the heavy chain variable domain includes analanine at position 35 in SEQ ID NO: 105; and a light chain variabledomain that that is at least 90% (e.g., at least 92%, at least 94%, atleast 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:106, where the light chain variable domain includes a histidine at anyof the specific combinations of one or more amino acid positions in SEQID NO: 106 listed in Table 4.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 106, where the lightchain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 106listed in Table 4, and where the light chain variable domain includes analanine at position 91 in SEQ ID NO: 106; and a heavy chain variabledomain that that is at least 90% (e.g., at least 92%, at least 94%, atleast 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:105, where the heavy chain variable domain includes a histidine at anyof the specific combinations of one or more amino acid positions in SEQID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 28 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising SEQ ID NO: 106, and a heavy chain variable domain that is atleast 90% identical (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 105, where theheavy chain variable domain includes a histidine at any of the specificcombinations of one or more (e.g., two, three, four, five, six, seven,eight, nine, or ten) amino acid positions in SEQ ID NO: 105 listed inTable 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 29 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 30 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 31 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 50 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes an alanine at position 91 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 92 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 93 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 94 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 95 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 106, wherein the light chainvariable domain includes a histidine at position 96 in SEQ ID NO: 106;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 105, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 105 listed in Table 3.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain ofSTRO-002 with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) histidine(s)substituted with an alanine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of STRO-002 with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) histidine(s) substituted with an alanine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of STRO-002 with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) histidines substituted with an alanine;and a light chain variable domain of STRO-002 with one or more (e.g.,one, two, three, four, five, six, seven, eight, nine, ten, eleven,twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen,nineteen, or twenty) histidine(s) substituted with an alanine. In someexamples of any of the ABPCs described herein, the heavy chain variabledomain of STRO-002 comprises SEQ ID NO: 105. In some examples of any ofthe ABPCs described herein, the light chain variable domain of STRO-002comprises SEQ ID NO: 106.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 107, SEQ ID NO: 108,and SEQ ID NO: 109, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 107-109 substituted with an alanine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 110, SEQ ID NO: 111,and SEQ ID NO: 112, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 110-112 substituted with an alanine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain includes: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 107, SEQ ID NO: 108,and SEQ ID NO: 109, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 107-109 substituted with an alanine;and a light chain variable domain comprising a CDR1, a CDR2, and a CDR3of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively,with collectively a total of one or more (e.g., one, two, three, four,five, six, seven, eight, nine, or ten) histidine(s) in SEQ ID NOs:110-112 substituted with an alanine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116,SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ IDNO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125,SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ IDNO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134,SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ IDNO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143,SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ IDNO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152,SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain of SEQ IDNO: 106, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160,SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ IDNO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169,SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ IDNO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178,SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, or SEQID NO: 183.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 106, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 157, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 158, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 159, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 160, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 161, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 162, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 163, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 164, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 165, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 166, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 167, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 168, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 169, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 170, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 171, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 172, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 173, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 174, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 175, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 176, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 177, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 178, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 179, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 180, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 181, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 182, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 183, and a heavy chain variable domain comprising SEQ ID NO:105, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO:121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO:130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO:139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO:148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain offarletuzumab with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) amino acidssubstituted with a histidine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of farletuzumab with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acids substituted with a histidine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of farletuzumab with one or more(e.g., one, two, three, four, five; six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acids substituted with a histidine;and a light chain variable domain of farletuzumab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acids substituted with a histidine.In some examples of any of the ABPCs described herein, the heavy chainvariable domain of farletuzumab comprises SEQ ID NO: 184. In someexamples of any of the ABPCs described herein, the light chain variabledomain of farletuzumab comprises SEQ ID NO: 185.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2; and a CDR3 of SEQ ID NO: 186, SEQ ID NO: 187,and SEQ ID NO: 188, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 186-188 substituted with ahistidine. In some examples of any of the ABPCs described herein, thefirst antigen-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 189, SEQ ID NO: 190,and SEQ ID NO: 191, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 189-191 substituted with ahistidine. In some examples of any of the ABPCs described herein, thefirst antigen-binding domain includes: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 186, SEQ ID NO: 187,and SEQ ID NO: 188, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) amino acid positions in SEQ ID NOs: 186-188 substituted with ahistidine; and a light chain variable domain comprising a CDR1, a CDR2,and a CDR3 of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191,respectively, with collectively a total of one or more (e.g., one, two,three, four, five, six, seven, eight, nine, or ten) amino acid positionsin SEQ ID NOs: 189-191 substituted with a histidine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 184 selected from the groupconsisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63,103, and 105. In some examples of any of the ABPCs described herein, thefirst antigen-binding domain includes a light chain variable domain thatis at least 90% (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 185, where thelight chain variable domain includes a histidine at one or more (e.g.,one, two, three, four, five, six, seven, eight, nine, ten, eleven,twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen,nineteen, or twenty) amino acid positions in SEQ ID NO: 185 selectedfrom the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92,94, 96, 97, 98, 99, and 100. In some examples of any of the ABPCsdescribed herein the first antigen-binding domain includes: a heavychain variable domain that is at least 90% (e.g., at least 92%, at least94%, at least 96%, at least 98%, at least 99%, or 100%) identical to SEQID NO: 184, where the heavy chain variable domain includes a histidineat one or more (e.g., one, two, three, four, five, six, seven, eight,nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 184 selected from the group consisting of: 26, 27, 28, 29, 30, 32,33, 34, 53, 56, 57, 59, 62, 63, 103, and 105, and a light chain variabledomain that is at least 90% (e.g., at least 92%, at least 94%, at least96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO: 185,where the light chain variable domain includes a histidine at one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) amino acid positions in SEQ ID NO: 185selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55,90, 92, 94, 96, 97, 98, 99, and 100.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 184, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes an alanine at position 99 in SEQ ID NO:184.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a heavy chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes an alanine at position 99 in SEQ ID NO:184, and a light chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 185, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 185 selected from the group consisting of: 29,33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 184 selected from the groupconsisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63,103, and 105, and where the heavy chain variable domain includes analanine at position 99 in SEQ ID NO: 184. In some examples of any of theABPCs described herein the first antigen-binding domain includes: aheavy chain variable domain that is at least 90% (e.g., at least 92%, atleast 94%, at least 96%, at least 98%, at least 99%, or 100%) identicalto SEQ ID NO: 184, where the heavy chain variable domain includes ahistidine at one or more (e.g., one, two, three, four, five, six, seven,eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 184 selected from the group consisting of: 26, 27, 28, 29, 30, 32,33, 34, 53, 56, 57, 59, 62, 63, 103, and 105, and where the heavy chainvariable domain includes an alanine at position 99 in SEQ ID NO: 184,and a light chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 185, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 185 selected from the group consisting of: 29,33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and 100.

In some examples of any of the ABPCs described herein, a heavy chainvariable domain includes a heavy chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 184, where the heavy chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 184 listed in Table 5and where the heavy chain variable domain includes an alanine atposition 99 of SEQ ID NO: 184.

TABLE 5 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 184that can be Substituted with Histidine 26 + 27, 26 + 28, 26 + 29, 26 +30, 26 + 32, 26 + 33, 26 + 34, 26 + 53, 26 + 56, 26 + 57, 26 + 59, 26 +62, 26 + 63, 26 + 103, 26 + 105, 27 + 28, 27 + 29, 27 + 30, 27 + 32,27 + 33, 27 + 34, 27 + 53, 27 + 56, 27 + 57, 27 + 59, 27 + 62, 27 + 63,27 + 103, 27 + 105, 28 + 29, 28 + 30, 28 + 32, 28 + 33, 28 + 34, 28 +53, 28 + 56, 28 + 57, 28 + 59, 28 + 62, 28 + 63, 28 + 103, 28 + 105,29 + 30, 29 + 32, 29 + 33, 29 + 34, 29 + 53, 29 + 56, 29 + 57, 29 + 59,29 + 62, 29 + 63, 29 + 103, 29 + 105, 30 + 32, 30 + 33, 30 + 34, 30 +53, 30 + 56, 30 + 57, 30 + 59, 30 + 62, 30 + 63, 30 + 103, 30 + 105,32 + 33, 32 + 34, 32 + 53, 32 + 56, 32 + 57, 32 + 59, 32 + 62, 32 + 63,32 + 103, 32 + 105, 33 + 34, 33 + 53, 33 + 56, 33 + 57, 33 + 59, 33 +62, 33 + 63, 33 + 103, 33 + 105, 34 + 53, 34 + 56, 34 + 57, 34 + 59,34 + 62, 34 + 63, 34 + 103, 34 + 105, 53 + 56, 53 + 57, 53 + 59, 53 +62, 53 + 63, 53 + 103, 53 + 105, 56 + 57, 56 + 59, 56 + 62, 56 + 63,56 + 103, 56 + 105, 57 + 59, 57 + 62, 57 + 63, 57 + 103, 57 + 105, 59 +62, 59 + 63, 59 + 103, 59 + 105, 62 + 63, 62 + 103, 62 + 105, 63 + 103,63 + 105, 103 + 105, 26 + 27 + 28, 26 + 27 + 29, 26 + 27 + 30, 26 + 27 +32, 26 + 27 + 33, 26 + 27 + 34, 26 + 27 + 53, 26 + 27 + 56, 26 + 27 +57, 26 + 27 + 59, 26 + 27 + 62, 26 + 27 + 63, 26 + 27 + 103, 26 + 27 +105, 26 + 28 + 29, 26 + 28 + 30, 26 + 28 + 32, 26 + 28 + 33, 26 + 28 +34, 26 + 28 + 53, 26 + 28 + 56, 26 + 28 + 57, 26 + 28 + 59, 26 + 28 +62, 26 + 28 + 63, 26 + 28 + 103, 26 + 28 + 105, 26 + 29 + 30, 26 + 29 +32, 26 + 29 + 33, 26 + 29 + 34, 26 + 29 + 53, 26 + 29 + 56, 26 + 29 +57, 26 + 29 + 59, 26 + 29 + 62, 26 + 29 + 63, 26 + 29 + 103, 26 + 29 +105, 26 + 30 + 32, 26 + 30 + 33, 26 + 30 + 34, 26 + 30 + 53, 26 + 30 +56, 26 + 30 + 57, 26 + 30 + 59, 26 + 30 + 62, 26 + 30 + 63, 26 + 30 +103, 26 + 30 + 105, 26 + 32 + 33, 26 + 32 + 34, 26 + 32 + 53, 26 + 32 +56, 26 + 32 + 57, 26 + 32 + 59, 26 + 32 + 62, 26 + 32 + 63, 26 + 32 +103, 26 + 32 + 105, 26 + 33 + 34, 26 + 33 + 53, 26 + 33 + 56, 26 + 33 +57, 26 + 33 + 59, 26 + 33 + 62, 26 + 33 + 63, 26 + 33 + 103, 26 + 33 +105, 26 + 34 + 53, 26 + 34 + 56, 26 + 34 + 57, 26 + 34 + 59, 26 + 34 +62, 26 + 34 + 63, 26 + 34 + 103, 26 + 34 + 105, 26 + 53 + 56, 26 + 53 +57, 26 + 53 + 59, 26 + 53 + 62, 26 + 53 + 63, 26 + 53 + 103, 26 + 53 +105, 26 + 56 + 57, 26 + 56 + 59, 26 + 56 + 62, 26 + 56 + 63, 26 + 56 +103, 26 + 56 + 105, 26 + 57 + 59, 26 + 57 + 62, 26 + 57 + 63, 26 + 57 +103, 26 + 57 + 105, 26 + 59 + 62, 26 + 59 + 63, 26 + 59 + 103, 26 + 59 +105, 26 + 62 + 63, 26 + 62 + 103, 26 + 62 + 105, 26 + 63 + 103, 26 +63 + 105, 26 + 103 + 105, 27 + 28 + 29, 27 + 28 + 30, 27 + 28 + 32, 27 +28 + 33, 27 + 28 + 34, 27 + 28 + 53, 27 + 28 + 56, 27 + 28 + 57, 27 +28 + 59, 27 + 28 + 62, 27 + 28 + 63, 27 + 28 + 103, 27 + 28 + 105, 27 +29 + 30, 27 + 29 + 32, 27 + 29 + 33, 27 + 29 + 34, 27 + 29 + 53, 27 +29 + 56, 27 + 29 + 57, 27 + 29 + 59, 27 + 29 + 62, 27 + 29 + 63, 27 +29 + 103, 27 + 29 + 105, 27 + 30 + 32, 27 + 30 + 33, 27 + 30 + 34, 27 +30 + 53, 27 + 30 + 56, 27 + 30 + 57, 27 + 30 + 59, 27 + 30 + 62, 27 +30 + 63, 27 + 30 + 103, 27 + 30 + 105, 27 + 32 + 33, 27 + 32 + 34, 27 +32 + 53, 27 + 32 + 56, 27 + 32 + 57, 27 + 32 + 59, 27 + 32 + 62, 27 +32 + 63, 27 + 32 + 103, 27 + 32 + 105, 27 + 33 + 34, 27 + 33 + 53, 27 +33 + 56, 27 + 33 + 57, 27 + 33 + 59, 27 + 33 + 62, 27 + 33 + 63, 27 +33 + 103, 27 + 33 + 105, 27 + 34 + 53, 27 + 34 + 56, 27 + 34 + 57, 27 +34 + 59, 27 + 34 + 62, 27 + 34 + 63, 27 + 34 + 103, 27 + 34 + 105, 27 +53 + 56, 27 + 53 + 57, 27 + 53 + 59, 27 + 53 + 62, 27 + 53 + 63, 27 +53 + 103, 27 + 53 + 105, 27 + 56 + 57, 27 + 56 + 59, 27 + 56 + 62, 27 +56 + 63, 27 + 56 + 103, 27 + 56 + 105, 27 + 57 + 59, 27 + 57 + 62, 27 +57 + 63, 27 + 57 + 103, 27 + 57 + 105, 27 + 59 + 62, 27 + 59 + 63, 27 +59 + 103, 27 + 59 + 105, 27 + 62 + 63, 27 + 62 + 103, 27 + 62 + 105,27 + 63 + 103, 27 + 63 + 105, 27 + 103 + 105, 28 + 29 + 30, 28 + 29 +32, 28 + 29 + 33, 28 + 29 + 34, 28 + 29 + 53, 28 + 29 + 56, 28 + 29 +57, 28 + 29 + 59, 28 + 29 + 62, 28 + 29 + 63, 28 + 29 + 103, 28 + 29 +105, 28 + 30 + 32, 28 + 30 + 33, 28 + 30 + 34, 28 + 30 + 53, 28 + 30 +56, 28 + 30 + 57, 28 + 30 + 59, 28 + 30 + 62, 28 + 30 + 63, 28 + 30 +103, 28 + 30 + 105, 28 + 32 + 33, 28 + 32 + 34, 28 + 32 + 53, 28 + 32 +56, 28 + 32 + 57, 28 + 32 + 59, 28 + 32 + 62, 28 + 32 + 63, 28 + 32 +103, 28 + 32 + 105, 28 + 33 + 34, 28 + 33 + 53, 28 + 33 + 56, 28 + 33 +57, 28 + 33 + 59, 28 + 33 + 62, 28 + 33 + 63, 28 + 33 + 103, 28 + 33 +105, 28 + 34 + 53, 28 + 34 + 56, 28 + 34 + 57, 28 + 34 + 59, 28 + 34 +62, 28 + 34 + 63, 28 + 34 + 103, 28 + 34 + 105, 28 + 53 + 56, 28 + 53 +57, 28 + 53 + 59, 28 + 53 + 62, 28 + 53 + 63, 28 + 53 + 103, 28 + 53 +105, 28 + 56 + 57, 28 + 56 + 59, 28 + 56 + 62, 28 + 56 + 63, 28 + 56 +103, 28 + 56 + 105, 28 + 57 + 59, 28 + 57 + 62, 28 + 57 + 63, 28 + 57 +103, 28 + 57 + 105, 28 + 59 + 62, 28 + 59 + 63, 28 + 59 + 103, 28 + 59 +105, 28 + 62 + 63, 28 + 62 + 103, 28 + 62 + 105, 28 + 63 + 103, 28 +63 + 105, 28 + 103 + 105, 29 + 30 + 32, 29 + 30 + 33, 29 + 30 + 34, 29 +30 + 53, 29 + 30 + 56, 29 + 30 + 57, 29 + 30 + 59, 29 + 30 + 62, 29 +30 + 63, 29 + 30 + 103, 29 + 30 + 105, 29 + 32 + 33, 29 + 32 + 34, 29 +32 + 53, 29 + 32 + 56, 29 + 32 + 57, 29 + 32 + 59, 29 + 32 + 62, 29 +32 + 63, 29 + 32 + 103, 29 + 32 + 105, 29 + 33 + 34, 29 + 33 + 53, 29 +33 + 56, 29 + 33 + 57, 29 + 33 + 59, 29 + 33 + 62, 29 + 33 + 63, 29 +33 + 103, 29 + 33 + 105, 29 + 34 + 53, 29 + 34 + 56, 29 + 34 + 57, 29 +34 + 59, 29 + 34 + 62, 29 + 34 + 63, 29 + 34 + 103, 29 + 34 + 105, 29 +53 + 56, 29 + 53 + 57, 29 + 53 + 59, 29 + 53 + 62, 29 + 53 + 63, 29 +53 + 103, 29 + 53 + 105, 29 + 56 + 57, 29 + 56 + 59, 29 + 56 + 62, 29 +56 + 63, 29 + 56 + 103, 29 + 56 + 105, 29 + 57 + 59, 29 + 57 + 62, 29 +57 + 63, 29 + 57 + 103, 29 + 57 + 105, 29 + 59 + 62, 29 + 59 + 63, 29 +59 + 103, 29 + 59 + 105, 29 + 62 + 63, 29 + 62 + 103, 29 + 62 + 105,29 + 63 + 103, 29 + 63 + 105, 29 + 103 + 105, 30 + 32 + 33, 30 + 32 +34, 30 + 32 + 53, 30 + 32 + 56, 30 + 32 + 57, 30 + 32 + 59, 30 + 32 +62, 30 + 32 + 63, 30 + 32 + 103, 30 + 32 + 105, 30 + 33 + 34, 30 + 33 +53, 30 + 33 + 56, 30 + 33 + 57, 30 + 33 + 59, 30 + 33 + 62, 30 + 33 +63, 30 + 33 + 103, 30 + 33 + 105, 30 + 34 + 53, 30 + 34 + 56, 30 + 34 +57, 30 + 34 + 59, 30 + 34 + 62, 30 + 34 + 63, 30 + 34 + 103, 30 + 34 +105, 30 + 53 + 56, 30 + 53 + 57, 30 + 53 + 59, 30 + 53 + 62, 30 + 53 +63, 30 + 53 + 103, 30 + 53 + 105, 30 + 56 + 57, 30 + 56 + 59, 30 + 56 +62, 30 + 56 + 63, 30 + 56 + 103, 30 + 56 + 105, 30 + 57 + 59, 30 + 57 +62, 30 + 57 + 63, 30 + 57 + 103, 30 + 57 + 105, 30 + 59 + 62, 30 + 59 +63, 30 + 59 + 103, 30 + 59 + 105, 30 + 62 + 63, 30 + 62 + 103, 30 + 62 +105, 30 + 63 + 103, 30 + 63 + 105, 30 + 103 + 105, 32 + 33 + 34, 32 +33 + 53, 32 + 33 + 56, 32 + 33 + 57, 32 + 33 + 59, 32 + 33 + 62, 32 +33 + 63, 32 + 33 + 103, 32 + 33 + 105, 32 + 34 + 53, 32 + 34 + 56, 32 +34 + 57, 32 + 34 + 59, 32 + 34 + 62, 32 + 34 + 63, 32 + 34 + 103, 32 +34 + 105, 32 + 53 + 56, 32 + 53 + 57, 32 + 53 + 59, 32 + 53 + 62, 32 +53 + 63, 32 + 53 + 103, 32 + 53 + 105, 32 + 56 + 57, 32 + 56 + 59, 32 +56 + 62, 32 + 56 + 63, 32 + 56 + 103, 32 + 56 + 105, 32 + 57 + 59, 32 +57 + 62, 32 + 57 + 63, 32 + 57 + 103, 32 + 57 + 105, 32 + 59 + 62, 32 +59 + 63, 32 + 59 + 103, 32 + 59 + 105, 32 + 62 + 63, 32 + 62 + 103, 32 +62 + 105, 32 + 63 + 103, 32 + 63 + 105, 32 + 103 + 105, 33 + 34 + 53,33 + 34 + 56, 33 + 34 + 57, 33 + 34 + 59, 33 + 34 + 62, 33 + 34 + 63,33 + 34 + 103, 33 + 34 + 105, 33 + 53 + 56, 33 + 53 + 57, 33 + 53 + 59,33 + 53 + 62, 33 + 53 + 63, 33 + 53 + 103, 33 + 53 + 105, 33 + 56 + 57,33 + 56 + 59, 33 + 56 + 62, 33 + 56 + 63, 33 + 56 + 103, 33 + 56 + 105,33 + 57 + 59, 33 + 57 + 62, 33 + 57 + 63, 33 + 57 + 103, 33 + 57 + 105,33 + 59 + 62, 33 + 59 + 63, 33 + 59 + 103, 33 + 59 + 105, 33 + 62 + 63,33 + 62 + 103, 33 + 62 + 105, 33 + 63 + 103, 33 + 63 + 105, 33 + 103 +105, 34 + 53 + 56, 34 + 53 + 57, 34 + 53 + 59, 34 + 53 + 62, 34 + 53 +63, 34 + 53 + 103, 34 + 53 + 105, 34 + 56 + 57, 34 + 56 + 59, 34 + 56 +62, 34 + 56 + 63, 34 + 56 + 103, 34 + 56 + 105, 34 + 57 + 59, 34 + 57 +62, 34 + 57 + 63, 34 + 57 + 103, 34 + 57 + 105, 34 + 59 + 62, 34 + 59 +63, 34 + 59 + 103, 34 + 59 + 105, 34 + 62 + 63, 34 + 62 + 103, 34 + 62 +105, 34 + 63 + 103, 34 + 63 + 105, 34 + 103 + 105, 53 + 56 + 57, 53 +56 + 59, 53 + 56 + 62, 53 + 56 + 63, 53 + 56 + 103, 53 + 56 + 105, 53 +57 + 59, 53 + 57 + 62, 53 + 57 + 63, 53 + 57 + 103, 53 + 57 + 105, 53 +59 + 62, 53 + 59 + 63, 53 + 59 + 103, 53 + 59 + 105, 53 + 62 + 63, 53 +62 + 103, 53 + 62 + 105, 53 + 63 + 103, 53 + 63 + 105, 53 + 103 + 105,56 + 57 + 59, 56 + 57 + 62, 56 + 57 + 63, 56 + 57 + 103, 56 + 57 + 105,56 + 59 + 62, 56 + 59 + 63, 56 + 59 + 103, 56 + 59 + 105, 56 + 62 + 63,56 + 62 + 103, 56 + 62 + 105, 56 + 63 + 103, 56 + 63 + 105, 56 + 103 +105, 57 + 59 + 62, 57 + 59 + 63, 57 + 59 + 103, 57 + 59 + 105, 57 + 62 +63, 57 + 62 + 103, 57 + 62 + 105, 57 + 63 + 103, 57 + 63 + 105, 57 +103 + 105, 59 + 62 + 63, 59 + 62 + 103, 59 + 62 + 105, 59 + 63 + 103,59 + 63 + 105, 59 + 103 + 105, 62 + 63 + 103, 62 + 63 + 105, 62 + 103 +105, 63 + 103 + 105,

In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 185, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 185 listed in Table 6.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 185, where the lightchain variable domain includes an alanine at position 35 in SEQ ID NO:185.

In some examples of any of the ABPCs described herein the firstantigen-binding domain includes: a light chain variable domain that isat least 90% (e.g., at least 92%, at least 94%, at least 96%, at least98%, at least 99%, or 100%) identical to SEQ ID NO: 185, where the lightchain variable domain includes an alanine at position 35 in SEQ ID NO:185, and a heavy chain variable domain that is at least 90% (e.g., atleast 92%, at least 94%, at least 96%, at least 98%, at least 99%, or100%) identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 184 selected from the group consisting of: 26,27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 185, where the lightchain variable domain includes a histidine at one or more (e.g., one,two, three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) amino acid positions in SEQ ID NO: 185 selected from the groupconsisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98,99, and 100, and where the light chain variable domain includes analanine at position 35 in SEQ ID NO: 185. In some examples of any of theABPCs described herein the first antigen-binding domain includes: alight chain variable domain that is at least 90% (e.g., at least 92%, atleast 94%, at least 96%, at least 98%, at least 99%, or 100%) identicalto SEQ ID NO: 185, where the light chain variable domain includes ahistidine at one or more (e.g., one, two, three, four, five, six, seven,eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen,seventeen, eighteen, nineteen, or twenty) amino acid positions in SEQ IDNO: 185 selected from the group consisting of: 29, 33, 34, 51, 52, 53,54, 55, 90, 92, 94, 96, 97, 98, 99, and 100, and where the light chainvariable domain includes an alanine at position 35 in SEQ ID NO: 185,and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the light chain variable domainincludes a histidine at one or more (e.g., one, two, three, four, five,six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen,fifteen, sixteen, seventeen, eighteen, nineteen, or twenty) amino acidpositions in SEQ ID NO: 184 selected from the group consisting of: 26,27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105.

In some examples of any of the ABPCs described herein, a light chainvariable domain includes a light chain variable domain that is at least90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%, atleast 99%, or 100%) identical to SEQ ID NO: 185, where the light chainvariable domain includes a histidine at any of the specific combinationsof one or more amino acid positions in SEQ ID NO: 185 listed in Table 6and where the light chain variable domain includes an alanine atposition 35 of SEQ ID NO: 185.

TABLE 6 Exemplary Combinations of Amino Acid Positions in SEQ ID NO: 185that can be Substituted with Histidine 29 + 33, 29 + 34, 29 + 51, 29 +52, 29 + 53, 29 + 54, 29 + 55, 29 + 90, 29 + 92, 29 + 94, 29 + 96, 29 +97, 29 + 98, 29 + 99, 29 + 100, 33 + 34, 33 + 51, 33 + 52, 33 + 53, 33 +54, 33 + 55, 33 + 90, 33 + 92, 33 + 94, 33 + 96, 33 + 97, 33 + 98, 33 +99, 33 + 100, 34 + 51, 34 + 52, 34 + 53, 34 + 54, 34 + 55, 34 + 90, 34 +92, 34 + 94, 34 + 96, 34 + 97, 34 + 98, 34 + 99, 34 + 100, 51 + 52, 51 +53, 51 + 54, 51 + 55, 51 + 90, 51 + 92, 51 + 94, 51 + 96, 51 + 97, 51 +98, 51 + 99, 51 + 100, 52 + 53, 52 + 54, 52 + 55, 52 + 90, 52 + 92, 52 +94, 52 + 96, 52 + 97, 52 + 98, 52 + 99, 52 + 100, 53 + 54, 53 + 55, 53 +90, 53 + 92, 53 + 94, 53 + 96, 53 + 97, 53 + 98, 53 + 99, 53 + 100, 54 +55, 54 + 90, 54 + 92, 54 + 94, 54 + 96, 54 + 97, 54 + 98, 54 + 99, 54 +100, 55 + 90, 55 + 92, 55 + 94, 55 + 96, 55 + 97, 55 + 98, 55 + 99, 55 +100, 90 + 92, 90 + 94, 90 + 96, 90 + 97, 90 + 98, 90 + 99, 90 + 100,92 + 94, 92 + 96, 92 + 97, 92 + 98, 92 + 99, 92 + 100, 94 + 96, 94 + 97,94 + 98, 94 + 99, 94 + 100, 96 + 97, 96 + 98, 96 + 99, 96 + 100, 97 +98, 97 + 99, 97 + 100, 98 + 99, 98 + 100, 99 + 100, 29 + 33 + 34, 29 +33 + 51, 29 + 33 + 52, 29 + 33 + 53, 29 + 33 + 54, 29 + 33 + 55, 29 +33 + 90, 29 + 33 + 92, 29 + 33 + 94, 29 + 33 + 96, 29 + 33 + 97, 29 +33 + 98, 29 + 33 + 99, 29 + 33 + 100, 29 + 34 + 51, 29 + 34 + 52, 29 +34 + 53, 29 + 34 + 54, 29 + 34 + 55, 29 + 34 + 90, 29 + 34 + 92, 29 +34 + 94, 29 + 34 + 96, 29 + 34 + 97, 29 + 34 + 98, 29 + 34 + 99, 29 +34 + 100, 29 + 51 + 52, 29 + 51 + 53, 29 + 51 + 54, 29 + 51 + 55, 29 +51 + 90, 29 + 51 + 92, 29 + 51 + 94, 29 + 51 + 96, 29 + 51 + 97, 29 +51 + 98, 29 + 51 + 99, 29 + 51 + 100, 29 + 52 + 53, 29 + 52 + 54, 29 +52 + 55, 29 + 52 + 90, 29 + 52 + 92, 29 + 52 + 94, 29 + 52 + 96, 29 +52 + 97, 29 + 52 + 98, 29 + 52 + 99, 29 + 52 + 100, 29 + 53 + 54, 29 +53 + 55, 29 + 53 + 90, 29 + 53 + 92, 29 + 53 + 94, 29 + 53 + 96, 29 +53 + 97, 29 + 53 + 98, 29 + 53 + 99, 29 + 53 + 100, 29 + 54 + 55, 29 +54 + 90, 29 + 54 + 92, 29 + 54 + 94, 29 + 54 + 96, 29 + 54 + 97, 29 +54 + 98, 29 + 54 + 99, 29 + 54 + 100, 29 + 55 + 90, 29 + 55 + 92, 29 +55 + 94, 29 + 55 + 96, 29 + 55 + 97, 29 + 55 + 98, 29 + 55 + 99, 29 +55 + 100, 29 + 90 + 92, 29 + 90 + 94, 29 + 90 + 96, 29 + 90 + 97, 29 +90 + 98, 29 + 90 + 99, 29 + 90 + 100, 29 + 92 + 94, 29 + 92 + 96, 29 +92 + 97, 29 + 92 + 98, 29 + 92 + 99, 29 + 92 + 100, 29 + 94 + 96, 29 +94 + 97, 29 + 94 + 98, 29 + 94 + 99, 29 + 94 + 100, 29 + 96 + 97, 29 +96 + 98, 29 + 96 + 99, 29 + 96 + 100, 29 + 97 + 98, 29 + 97 + 99, 29 +97 + 100, 29 + 98 + 99, 29 + 98 + 100, 29 + 99 + 100, 33 + 34 + 51, 33 +34 + 52, 33 + 34 + 53, 33 + 34 + 54, 33 + 34 + 55, 33 + 34 + 90, 33 +34 + 92, 33 + 34 + 94, 33 + 34 + 96, 33 + 34 + 97, 33 + 34 + 98, 33 +34 + 99, 33 + 34 + 100, 33 + 51 + 52, 33 + 51 + 53, 33 + 51 + 54, 33 +51 + 55, 33 + 51 + 90, 33 + 51 + 92, 33 + 51 + 94, 33 + 51 + 96, 33 +51 + 97, 33 + 51 + 98, 33 + 51 + 99, 33 + 51 + 100, 33 + 52 + 53, 33 +52 + 54, 33 + 52 + 55, 33 + 52 + 90, 33 + 52 + 92, 33 + 52 + 94, 33 +52 + 96, 33 + 52 + 97, 33 + 52 + 98, 33 + 52 + 99, 33 + 52 + 100, 33 +53 + 54, 33 + 53 + 55, 33 + 53 + 90, 33 + 53 + 92, 33 + 53 + 94, 33 +53 + 96, 33 + 53 + 97, 33 + 53 + 98, 33 + 53 + 99, 33 + 53 + 100, 33 +54 + 55, 33 + 54 + 90, 33 + 54 + 92, 33 + 54 + 94, 33 + 54 + 96, 33 +54 + 97, 33 + 54 + 98, 33 + 54 + 99, 33 + 54 + 100, 33 + 55 + 90, 33 +55 + 92, 33 + 55 + 94, 33 + 55 + 96, 33 + 55 + 97, 33 + 55 + 98, 33 +55 + 99, 33 + 55 + 100, 33 + 90 + 92, 33 + 90 + 94, 33 + 90 + 96, 33 +90 + 97, 33 + 90 + 98, 33 + 90 + 99, 33 + 90 + 100, 33 + 92 + 94, 33 +92 + 96, 33 + 92 + 97, 33 + 92 + 98, 33 + 92 + 99, 33 + 92 + 100, 33 +94 + 96, 33 + 94 + 97, 33 + 94 + 98, 33 + 94 + 99, 33 + 94 + 100, 33 +96 + 97, 33 + 96 + 98, 33 + 96 + 99, 33 + 96 + 100, 33 + 97 + 98, 33 +97 + 99, 33 + 97 + 100, 33 + 98 + 99, 33 + 98 + 100, 33 + 99 + 100, 34 +51 + 52, 34 + 51 + 53, 34 + 51 + 54, 34 + 51 + 55, 34 + 51 + 90, 34 +51 + 92, 34 + 51 + 94, 34 + 51 + 96, 34 + 51 + 97, 34 + 51 + 98, 34 +51 + 99, 34 + 51 + 100, 34 + 52 + 53, 34 + 52 + 54, 34 + 52 + 55, 34 +52 + 90, 34 + 52 + 92, 34 + 52 + 94, 34 + 52 + 96, 34 + 52 + 97, 34 +52 + 98, 34 + 52 + 99, 34 + 52 + 100, 34 + 53 + 54, 34 + 53 + 55, 34 +53 + 90, 34 + 53 + 92, 34 + 53 + 94, 34 + 53 + 96, 34 + 53 + 97, 34 +53 + 98, 34 + 53 + 99, 34 + 53 + 100, 34 + 54 + 55, 34 + 54 + 90, 34 +54 + 92, 34 + 54 + 94, 34 + 54 + 96, 34 + 54 + 97, 34 + 54 + 98, 34 +54 + 99, 34 + 54 + 100, 34 + 55 + 90, 34 + 55 + 92, 34 + 55 + 94, 34 +55 + 96, 34 + 55 + 97, 34 + 55 + 98, 34 + 55 + 99, 34 + 55 + 100, 34 +90 + 92, 34 + 90 + 94, 34 + 90 + 96, 34 + 90 + 97, 34 + 90 + 98, 34 +90 + 99, 34 + 90 + 100, 34 + 92 + 94, 34 + 92 + 96, 34 + 92 + 97, 34 +92 + 98, 34 + 92 + 99, 34 + 92 + 100, 34 + 94 + 96, 34 + 94 + 97, 34 +94 + 98, 34 + 94 + 99, 34 + 94 + 100, 34 + 96 + 97, 34 + 96 + 98, 34 +96 + 99, 34 + 96 + 100, 34 + 97 + 98, 34 + 97 + 99, 34 + 97 + 100, 34 +98 + 99, 34 + 98 + 100, 34 + 99 + 100, 51 + 52 + 53, 51 + 52 + 54, 51 +52 + 55, 51 + 52 + 90, 51 + 52 + 92, 51 + 52 + 94, 51 + 52 + 96, 51 +52 + 97, 51 + 52 + 98, 51 + 52 + 99, 51 + 52 + 100, 51 + 53 + 54, 51 +53 + 55, 51 + 53 + 90, 51 + 53 + 92, 51 + 53 + 94, 51 + 53 + 96, 51 +53 + 97, 51 + 53 + 98, 51 + 53 + 99, 51 + 53 + 100, 51 + 54 + 55, 51 +54 + 90, 51 + 54 + 92, 51 + 54 + 94, 51 + 54 + 96, 51 + 54 + 97, 51 +54 + 98, 51 + 54 + 99, 51 + 54 + 100, 51 + 55 + 90, 51 + 55 + 92, 51 +55 + 94, 51 + 55 + 96, 51 + 55 + 97, 51 + 55 + 98, 51 + 55 + 99, 51 +55 + 100, 51 + 90 + 92, 51 + 90 + 94, 51 + 90 + 96, 51 + 90 + 97, 51 +90 + 98, 51 + 90 + 99, 51 + 90 + 100, 51 + 92 + 94, 51 + 92 + 96, 51 +92 + 97, 51 + 92 + 98, 51 + 92 + 99, 51 + 92 + 100, 51 + 94 + 96, 51 +94 + 97, 51 + 94 + 98, 51 + 94 + 99, 51 + 94 + 100, 51 + 96 + 97, 51 +96 + 98, 51 + 96 + 99, 51 + 96 + 100, 51 + 97 + 98, 51 + 97 + 99, 51 +97 + 100, 51 + 98 + 99, 51 + 98 + 100, 51 + 99 + 100, 52 + 53 + 54, 52 +53 + 55, 52 + 53 + 90, 52 + 53 + 92, 52 + 53 + 94, 52 + 53 + 96, 52 +53 + 97, 52 + 53 + 98, 52 + 53 + 99, 52 + 53 + 100, 52 + 54 + 55, 52 +54 + 90, 52 + 54 + 92, 52 + 54 + 94, 52 + 54 + 96, 52 + 54 + 97, 52 +54 + 98, 52 + 54 + 99, 52 + 54 + 100, 52 + 55 + 90, 52 + 55 + 92, 52 +55 + 94, 52 + 55 + 96, 52 + 55 + 97, 52 + 55 + 98, 52 + 55 + 99, 52 +55 + 100, 52 + 90 + 92, 52 + 90 + 94, 52 + 90 + 96, 52 + 90 + 97, 52 +90 + 98, 52 + 90 + 99, 52 + 90 + 100, 52 + 92 + 94, 52 + 92 + 96, 52 +92 + 97, 52 + 92 + 98, 52 + 92 + 99, 52 + 92 + 100, 52 + 94 + 96, 52 +94 + 97, 52 + 94 + 98, 52 + 94 + 99, 52 + 94 + 100, 52 + 96 + 97, 52 +96 + 98, 52 + 96 + 99, 52 + 96 + 100, 52 + 97 + 98, 52 + 97 + 99, 52 +97 + 100, 52 + 98 + 99, 52 + 98 + 100, 52 + 99 + 100, 53 + 54 + 55, 53 +54 + 90, 53 + 54 + 92, 53 + 54 + 94, 53 + 54 + 96, 53 + 54 + 97, 53 +54 + 98, 53 + 54 + 99, 53 + 54 + 100, 53 + 55 + 90, 53 + 55 + 92, 53 +55 + 94, 53 + 55 + 96, 53 + 55 + 97, 53 + 55 + 98, 53 + 55 + 99, 53 +55 + 100, 53 + 90 + 92, 53 + 90 + 94, 53 + 90 + 96, 53 + 90 + 97, 53 +90 + 98, 53 + 90 + 99, 53 + 90 + 100, 53 + 92 + 94, 53 + 92 + 96, 53 +92 + 97, 53 + 92 + 98, 53 + 92 + 99, 53 + 92 + 100, 53 + 94 + 96, 53 +94 + 97, 53 + 94 + 98, 53 + 94 + 99, 53 + 94 + 100, 53 + 96 + 97, 53 +96 + 98, 53 + 96 + 99, 53 + 96 + 100, 53 + 97 + 98, 53 + 97 + 99, 53 +97 + 100, 53 + 98 + 99, 53 + 98 + 100, 53 + 99 + 100, 54 + 55 + 90, 54 +55 + 92, 54 + 55 + 94, 54 + 55 + 96, 54 + 55 + 97, 54 + 55 + 98, 54 +55 + 99, 54 + 55 + 100, 54 + 90 + 92, 54 + 90 + 94, 54 + 90 + 96, 54 +90 + 97, 54 + 90 + 98, 54 + 90 + 99, 54 + 90 + 100, 54 + 92 + 94, 54 +92 + 96, 54 + 92 + 97, 54 + 92 + 98, 54 + 92 + 99, 54 + 92 + 100, 54 +94 + 96, 54 + 94 + 97, 54 + 94 + 98, 54 + 94 + 99, 54 + 94 + 100, 54 +96 + 97, 54 + 96 + 98, 54 + 96 + 99, 54 + 96 + 100, 54 + 97 + 98, 54 +97 + 99, 54 + 97 + 100, 54 + 98 + 99, 54 + 98 + 100, 54 + 99 + 100, 55 +90 + 92, 55 + 90 + 94, 55 + 90 + 96, 55 + 90 + 97, 55 + 90 + 98, 55 +90 + 99, 55 + 90 + 100, 55 + 92 + 94, 55 + 92 + 96, 55 + 92 + 97, 55 +92 + 98, 55 + 92 + 99, 55 + 92 + 100, 55 + 94 + 96, 55 + 94 + 97, 55 +94 + 98, 55 + 94 + 99, 55 + 94 + 100, 55 + 96 + 97, 55 + 96 + 98, 55 +96 + 99, 55 + 96 + 100, 55 + 97 + 98, 55 + 97 + 99, 55 + 97 + 100, 55 +98 + 99, 55 + 98 + 100, 55 + 99 + 100, 90 + 92 + 94, 90 + 92 + 96, 90 +92 + 97, 90 + 92 + 98, 90 + 92 + 99, 90 + 92 + 100, 90 + 94 + 96, 90 +94 + 97, 90 + 94 + 98, 90 + 94 + 99, 90 + 94 + 100, 90 + 96 + 97, 90 +96 + 98, 90 + 96 + 99, 90 + 96 + 100, 90 + 97 + 98, 90 + 97 + 99, 90 +97 + 100, 90 + 98 + 99, 90 + 98 + 100, 90 + 99 + 100, 92 + 94 + 96, 92 +94 + 97, 92 + 94 + 98, 92 + 94 + 99, 92 + 94 + 100, 92 + 96 + 97, 92 +96 + 98, 92 + 96 + 99, 92 + 96 + 100, 92 + 97 + 98, 92 + 97 + 99, 92 +97 + 100, 92 + 98 + 99, 92 + 98 + 100, 92 + 99 + 100, 94 + 96 + 97, 94 +96 + 98, 94 + 96 + 99, 94 + 96 + 100, 94 + 97 + 98, 94 + 97 + 99, 94 +97 + 100, 94 + 98 + 99, 94 + 98 + 100, 94 + 99 + 100, 96 + 97 + 98, 96 +97 + 99, 96 + 97 + 100, 96 + 98 + 99, 96 + 98 + 100, 96 + 99 + 100, 97 +98 + 99, 97 + 98 + 100, 97 + 99 + 100, 98 + 99 + 100

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 184listed in Table 5; and a light chain variable domain that that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 186, where the lightchain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 185listed in Table 6.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 184listed in Table 5, and where the heavy chain variable domain includes analanine at position 99 in SEQ ID NO: 184; and a light chain variabledomain that that is at least 90% (e.g., at least 92%, at least 94%, atleast 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:185, where the light chain variable domain includes a histidine at anyof the specific combinations of one or more amino acid positions in SEQID NO: 185 listed in Table 6.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 184, where the heavychain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 184listed in Table 5, and where the heavy chain variable domain includes analanine at position 99 in SEQ ID NO: 184; and a light chain variabledomain that that is at least 90% (e.g., at least 92%, at least 94%, atleast 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:185, where the light chain variable domain includes a histidine at anyof the specific combinations of one or more amino acid positions in SEQID NO: 185 listed in Table 6.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain that is atleast 90% (e.g., at least 92%, at least 94%, at least 96%, at least 98%,at least 99%, or 100%) identical to SEQ ID NO: 185, where the lightchain variable domain includes a histidine at any of the specificcombinations of one or more amino acid positions in SEQ ID NO: 185listed in Table 6, and where the light chain variable domain includes analanine at position 35 in SEQ ID NO: 185; and a heavy chain variabledomain that that is at least 90% (e.g., at least 92%, at least 94%, atleast 96%, at least 98%, at least 99%, or 100%) identical to SEQ ID NO:184, where the heavy chain variable domain includes a histidine at anyof the specific combinations of one or more amino acid positions in SEQID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 29 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising SEQ ID NO: 185, and a heavy chain variable domain that is atleast 90% identical (e.g., at least 92%, at least 94%, at least 96%, atleast 98%, at least 99%, or 100%) identical to SEQ ID NO: 184, where theheavy chain variable domain includes a histidine at any of the specificcombinations of one or more (e.g., two, three, four, five, six, seven,eight, nine, or ten) amino acid positions in SEQ ID NO: 184 listed inTable 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 33 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 34 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes an alanine at position 35 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 51 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 52 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 53 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 54 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 55 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 90 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 92 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 94 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 96 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 97 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 98 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 99 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domain that isat least 90% identical to SEQ ID NO: 185, wherein the light chainvariable domain includes a histidine at position 100 in SEQ ID NO: 185;and a heavy chain variable domain that is at least 90% (e.g., at least92%, at least 94%, at least 96%, at least 98%, at least 99%, or 100%)identical to SEQ ID NO: 184, where the heavy chain variable domainincludes a histidine at any of the specific combinations of one or moreamino acid positions in SEQ ID NO: 184 listed in Table 5.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a heavy chain variable domain offarletuzumab with one or more (e.g., one, two, three, four, five, six,seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen,sixteen, seventeen, eighteen, nineteen, or twenty) histidine(s)substituted with an alanine. In some examples of any of the ABPCsdescribed herein, the first antigen-binding domain includes a lightchain variable domain of farletuzumab with one or more (e.g., one, two,three, four, five, six, seven, eight, nine, ten, eleven, twelve,thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, ortwenty) histidine(s) substituted with an alanine. In some examples ofany of the ABPCs described herein, the first antigen-binding domainincludes a heavy chain variable domain of farletuzumab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) histidines substituted with an alanine;and a light chain variable domain of farletuzumab with one or more(e.g., one, two, three, four, five, six, seven, eight, nine, ten,eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen,eighteen, nineteen, or twenty) histidine(s) substituted with an alanine.In some examples of any of the ABPCs described herein, the heavy chainvariable domain of farletuzumab comprises SEQ ID NO: 184. In someexamples of any of the ABPCs described herein, the light chain variabledomain of farletuzumab comprises SEQ ID NO: 185.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 186, SEQ ID NO: 187,and SEQ ID NO: 188, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 186-188 substituted with an alanine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 189, SEQ ID NO: 190,and SEQ ID NO: 191, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 189-191 substituted with an alanine. Insome examples of any of the ABPCs described herein, the firstantigen-binding domain includes: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NO: 186, SEQ ID NO: 187,and SEQ ID NO: 188, respectively, with collectively a total of one ormore (e.g., one, two, three, four, five, six, seven, eight, nine, orten) histidine(s) in SEQ ID NOs: 186-188 substituted with an alanine;and a light chain variable domain comprising a CDR1, a CDR2, and a CDR3of SEQ ID NO: 189, SEQ ID NO: 190, and SEQ ID NO: 191, respectively,with collectively a total of one or more (e.g., one, two, three, four,five, six, seven, eight, nine, or ten) histidine(s) in SEQ ID NOs:189-191 substituted with an alanine.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195,SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ IDNO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204,SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ IDNO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213,SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ IDNO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222,SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ IDNO: 227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain of SEQ IDNO: 185, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234,SEQ ID NO: 235, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ IDNO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243,SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ IDNO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252,SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, or SEQID NO: 257.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 185, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 231, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 232, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 233, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 234, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 235, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 236, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 237, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 238, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 239, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 240, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 241, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 242, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 243, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 244, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 245, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 246, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 247, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 248, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 249, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 250, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 251, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 252, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 253, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 254, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 255, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 256, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

In some examples of any of the ABPCs described herein, the firstantigen-binding domain includes a light chain variable domain comprisingSEQ ID NO: 257, and a heavy chain variable domain comprising SEQ ID NO:184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO:209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO:218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO:227, SEQ ID NO: 228, SEQ ID NO: 229, or SEQ ID NO: 230.

Also provided herein are pharmaceutical compositions including any ofthe ABPCs described herein. Also provided herein are methods of treatinga subject in need thereof that include administering a therapeuticallyeffective amount of any of the ABPCs described herein to the subject.

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 1%increase, at least a 2% increase, at least a 5% increase, at least a 10%increase, at least a 15% increase, at least a 20% increase, at least a25% increase, at least a 30% increase, at least a 35% increase, at leasta 40% increase, at least a 45% increase, at least a 50% increase, atleast a 55% increase, at least a 60% increase, at least a 65% increase,at least a 70% increase, at least a 75% increase, at least a 80%increase, at least a 85% increase, at least a 90% increase, at least a95% increase, at least a 100% increase, at least a 120% increase, atleast a 140% increase, at least a 160% increase, at least a 180%increase, at least a 200% increase, at least a 250% increase, at least a300% increase, at least a 350% increase, at least a 400% increase, atleast a 450% increase, at least a 500% increase, at least a 1,000%increase, at least a 2,000% increase, at least a 3,000% increase, atleast a 4,000% increase, at least a 5,000% increase, at least a 6,000%increase, at least a 7,000% increase, at least a 8,000% increase, at aleast a 9,000% increase, or at least a 10,000% increase, or about a 1%increase to about 10,000% increase, about a 1% increase to about a9,000% increase, about a 1% increase to about a 8,000% increase, about a1% increase to about a 7,000% increase, about a 1% increase to about a6,000% increase, about a 1% increase to about a 5,000% increase, about a1% increase to about a 4,000% increase, about a 1% increase to about a3,000% increase, about a 1% increase to about a 2,000% increase, about a1% increase to about a 1,000% increase, about a 1% increase to about a500% increase, about a 1% increase to about a 450% increase, about a 1%increase to about a 400% increase, about a 1% increase to about a 350%increase, about a 1% increase to about a 300% increase, about a 1%increase to about a 250% increase, about a 1% increase to about a 200%increase, about a 1% increase to about a 180% increase, about a 1%increase to about a 160% increase, about a 1% increase to about a 140%increase, about a 1% increase to about a 120% increase, about a 1%increase to about a 100% increase, about a 1% increase to about a 95%increase, about a 1% increase to about a 90% increase, about a 1%increase to about a 85% increase, about a 1% increase to about a 80%increase, about a 1% increase to about a 75% increase, about a 1%increase to about a 70% increase, about a 1% increase to about a 65%increase, about a 1% increase to about a 60% increase, about a 1%increase to about a 55% increase, about a 1% increase to about a 50%increase, about a 1% increase to about a 45% increase, about a 1%increase to about a 40% increase, about a 1% increase to about a 35%increase, about a 1% increase to about a 25% increase, about a 1%increase to about a 20% increase, about a 1% increase to about a 15%increase, about a 1% increase to about a 10% increase, about a 1%increase to about a 5% increase, about a 2% increase to about 10,000%increase, about a 2% increase to about a 9,000% increase, about a 2%increase to about a 8,000% increase, about a 2% increase to about a7,000% increase, about a 2% increase to about a 6,000% increase, about a2% increase to about a 5,000% increase, about a 2% increase to about a4,000% increase, about a 2% increase to about a 3,000% increase, about a2% increase to about a 2,000% increase, about a 2% increase to about a1,000% increase, about a 2% increase to about a 500% increase, about a2% increase to about a 450% increase, about a 2% increase to about a400% increase, about a 2% increase to about a 350% increase, about a 2%increase to about a 300% increase, about a 2% increase to about a 250%increase, about a 2% increase to about a 200% increase, about a 2%increase to about a 180% increase, about a 2% increase to about a 160%increase, about a 2% increase to about a 140% increase, about a 2%increase to about a 120% increase, about a 2% increase to about a 100%increase, about a 2% increase to about a 95% increase, about a 2%increase to about a 90% increase, about a 2% increase to about a 85%increase, about a 2% increase to about a 80% increase, about a 2%increase to about a 75% increase, about a 2% increase to about a 70%increase, about a 2% increase to about a 65% increase, about a 2%increase to about a 60% increase, about a 2% increase to about a 55%increase, about a 2% increase to about a 50% increase, about a 2%increase to about a 45% increase, about a 2% increase to about a 40%increase, about a 2% increase to about a 35% increase, about a 2%increase to about a 25% increase, about a 2% increase to about a 20%increase, about a 2% increase to about a 15% increase, about a 2%increase to about a 10% increase, about a 2% increase to about a 5%increase, about a 5% increase to about 10,000% increase, about a 5%increase to about a 9,000% increase, about a 5% increase to about a8,000% increase, about a 5% increase to about a 7,000% increase, about a5% increase to about a 6,000% increase, about a 5% increase to about a5,000% increase, about a 5% increase to about a 4,000% increase, about a5% increase to about a 3,000% increase, about a 5% increase to about a2,000% increase, about a 5% increase to about a 1,000% increase, about a5% increase to about a 500% increase, about a 5% increase to about a450% increase, about a 5% increase to about a 400% increase, about a 5%increase to about a 350% increase, about a 5% increase to about a 300%increase, about a 5% increase to about a 250% increase, about a 5%increase to about a 200% increase, about a 5% increase to about a 180%increase, about a 5% increase to about a 160% increase, about a 5%increase to about a 140% increase, about a 5% increase to about a 120%increase, about a 5% increase to about a 100% increase, about a 5%increase to about a 95% increase, about a 5% increase to about a 90%increase, about a 5% increase to about a 85% increase, about a 5%increase to about a 80% increase, about a 5% increase to about a 75%increase, about a 5% increase to about a 70% increase, about a 5%increase to about a 65% increase, about a 5% increase to about a 60%increase, about a 5% increase to about a 55% increase, about a 5%increase to about a 50% increase, about a 5% increase to about a 45%increase, about a 5% increase to about a 40% increase, about a 5%increase to about a 35% increase, about a 5% increase to about a 25%increase, about a 5% increase to about a 20% increase, about a 5%increase to about a 15% increase, about a 5% increase to about a 10%increase, about a 10% increase to about 10,000% increase, about a 10%increase to about a 9,000% increase, about a 10% increase to about a8,000% increase, about a 10% increase to about a 7,000% increase, abouta 10% increase to about a 6,000% increase, about a 10% increase to abouta 5,000% increase, about a 10% increase to about a 4,000% increase,about a 10% increase to about a 3,000% increase, about a 10% increase toabout a 2,000% increase, about a 10% increase to about a 1,000%increase, about a 10% increase to about a 500% increase, about a 10%increase to about a 450% increase, about a 10% increase to about a 400%increase, about a 10% increase to about a 350% increase, about a 10%increase to about a 300% increase, about a 10% increase to about a 250%increase, about a 10% increase to about a 200% increase, about a 10%increase to about a 180% increase, about a 10% increase to about a 160%increase, about a 10% increase to about a 140% increase, about a 10%increase to about a 120% increase, about a 10% increase to about a 100%increase, about a 10% increase to about a 95% increase, about a 10%increase to about a 90% increase, about a 10% increase to about a 85%increase, about a 10% increase to about a 80% increase, about a 10%increase to about a 75% increase, about a 10% increase to about a 70%increase, about a 10% increase to about a 65% increase, about a 10%increase to about a 60% increase, about a 10% increase to about a 55%increase, about a 10% increase to about a 50% increase, about a 10%increase to about a 45% increase, about a 10% increase to about a 40%increase, about a 10% increase to about a 35% increase, about a 10%increase to about a 30% increase, about a 10% increase to about a 25%increase, about a 10% increase to about a 20% increase, about a 10%increase to about a 15% increase, about a 15% increase to about 10,000%increase, about a 15% increase to about a 9,000% increase, about a 15%increase to about a 8,000% increase, about a 15% increase to about a7,000% increase, about a 15% increase to about a 6,000% increase, abouta 15% increase to about a 5,000% increase, about a 15% increase to abouta 4,000% increase, about a 15% increase to about a 3,000% increase,about a 15% increase to about a 2,000% increase, about a 15% increase toabout a 1,000% increase, about a 15% increase to about a 500% increase,about a 15% increase to about a 450% increase, about a 15% increase toabout a 400% increase, about a 15% increase to about a 350% increase,about a 15% increase to about a 300% increase, about a 15% increase toabout a 250% increase, about a 15% increase to about a 200% increase,about a 15% increase to about a 180% increase, about a 15% increase toabout a 160% increase, about a 15% increase to about a 140% increase,about a 15% increase to about a 120% increase, about a 15% increase toabout a 100% increase, about a 15% increase to about a 95% increase,about a 15% increase to about a 90% increase, about a 15% increase toabout a 85% increase, about a 15% increase to about a 80% increase,about a 15% increase to about a 75% increase, about a 15% increase toabout a 70% increase, about a 15% increase to about a 65% increase,about a 15% increase to about a 60% increase, about a 15% increase toabout a 55% increase, about a 15% increase to about a 50% increase,about a 15% increase to about a 45% increase, about a 15% increase toabout a 40% increase, about a 15% increase to about a 35% increase,about a 15% increase to about a 30% increase, about a 15% increase toabout a 25% increase, about a 15% increase to about a 20% increase,about a 20% increase to about 10,000% increase, about a 20% increase toabout a 9,000% increase, about a 20% increase to about a 8,000%increase, about a 20% increase to about a 7,000% increase, about a 20%increase to about a 6,000% increase, about a 20% increase to about a5,000% increase, about a 20% increase to about a 4,000% increase, abouta 20% increase to about a 3,000% increase, about a 20% increase to abouta 2,000% increase, about a 20% increase to about a 1,000% increase,about a 20% increase to about a 500% increase, about a 20% increase toabout a 450% increase, about a 20% increase to about a 400% increase,about a 20% increase to about a 350% increase, about a 20% increase toabout a 300% increase, about a 20% increase to about a 250% increase,about a 20% increase to about a 200% increase, about a 20% increase toabout a 180% increase, about a 20% increase to about a 160% increase,about a 20% increase to about a 140% increase, about a 20% increase toabout a 120% increase, about a 20% increase to about a 100% increase,about a 20% increase to about a 95% increase, about a 20% increase toabout a 90% increase, about a 20% increase to about a 85% increase,about a 20% increase to about a 80% increase, about a 20% increase toabout a 75% increase, about a 20% increase to about a 70% increase,about a 20% increase to about a 65% increase, about a 20% increase toabout a 60% increase, about a 20% increase to about a 55% increase,about a 20% increase to about a 50% increase, about a 20% increase toabout a 45% increase, about a 20% increase to about a 40% increase,about a 20% increase to about a 35% increase, about a 20% increase toabout a 30% increase, about a 20% increase to about a 25% increase,about a 25% increase to about 10,000% increase, about a 25% increase toabout a 9,000% increase, about a 25% increase to about a 8,000%increase, about a 25% increase to about a 7,000% increase, about a 25%increase to about a 6,000% increase, about a 25% increase to about a5,000% increase, about a 25% increase to about a 4,000% increase, abouta 25% increase to about a 3,000% increase, about a 25% increase to abouta 2,000% increase, about a 25% increase to about a 1,000% increase,about a 25% increase to about a 500% increase, about a 25% increase toabout a 450% increase, about a 25% increase to about a 400% increase,about a 25% increase to about a 350% increase, about a 25% increase toabout a 300% increase, about a 25% increase to about a 250% increase,about a 25% increase to about a 200% increase, about a 25% increase toabout a 180% increase, about a 25% increase to about a 160% increase,about a 25% increase to about a 140% increase, about a 25% increase toabout a 120% increase, about a 25% increase to about a 100% increase,about a 25% increase to about a 95% increase, about a 25% increase toabout a 90% increase, about a 25% increase to about a 85% increase,about a 25% increase to about a 80% increase, about a 25% increase toabout a 75% increase, about a 25% increase to about a 70% increase,about a 25% increase to about a 65% increase, about a 25% increase toabout a 60% increase, about a 25% increase to about a 55% increase,about a 25% increase to about a 50% increase, about a 25% increase toabout a 45% increase, about a 25% increase to about a 40% increase,about a 25% increase to about a 35% increase, about a 25% increase toabout a 30% increase, about a 30% increase to about 10,000% increase,about a 30% increase to about a 9,000% increase, about a 30% increase toabout a 8,000% increase, about a 30% increase to about a 7,000%increase, about a 30% increase to about a 6,000% increase, about a 30%increase to about a 5,000% increase, about a 30% increase to about a4,000% increase, about a 30% increase to about a 3,000% increase, abouta 30% increase to about a 2,000% increase, about a 30% increase to abouta 1,000% increase, about a 30% increase to about a 500% increase, abouta 30% increase to about a 450% increase, about a 30% increase to about a400% increase, about a 30% increase to about a 350% increase, about a30% increase to about a 300% increase, about a 30% increase to about a250% increase, about a 30% increase to about a 200% increase, about a30% increase to about a 180% increase, about a 30% increase to about a160% increase, about a 30% increase to about a 140% increase, about a30% increase to about a 120% increase, about a 30% increase to about a100% increase, about a 30% increase to about a 95% increase, about a 30%increase to about a 90% increase, about a 30% increase to about a 85%increase, about a 30% increase to about a 80% increase, about a 30%increase to about a 75% increase, about a 30% increase to about a 70%increase, about a 30% increase to about a 65% increase, about a 30%increase to about a 60% increase, about a 30% increase to about a 55%increase, about a 30% increase to about a 50% increase, about a 30%increase to about a 45% increase, about a 30% increase to about a 40%increase, about a 30% increase to about a 35% increase, about a 35%increase to about 10,000% increase, about a 35% increase to about a9,000% increase, about a 35% increase to about a 8,000% increase, abouta 35% increase to about a 7,000% increase, about a 35% increase to abouta 6,000% increase, about a 35% increase to about a 5,000% increase,about a 35% increase to about a 4,000% increase, about a 35% increase toabout a 3,000% increase, about a 35% increase to about a 2,000%increase, about a 35% increase to about a 1,000% increase, about a 35%increase to about a 500% increase, about a 35% increase to about a 450%increase, about a 35% increase to about a 400% increase, about a 35%increase to about a 350% increase, about a 35% increase to about a 300%increase, about a 35% increase to about a 250% increase, about a 35%increase to about a 200% increase, about a 35% increase to about a 180%increase, about a 35% increase to about a 160% increase, about a 35%increase to about a 140% increase, about a 35% increase to about a 120%increase, about a 35% increase to about a 100% increase, about a 35%increase to about a 95% increase, about a 35% increase to about a 90%increase, about a 35% increase to about a 85% increase, about a 35%increase to about a 80% increase, about a 35% increase to about a 75%increase, about a 35% increase to about a 70% increase, about a 35%increase to about a 65% increase, about a 35% increase to about a 60%increase, about a 35% increase to about a 55% increase, about a 35%increase to about a 50% increase, about a 35% increase to about a 45%increase, about a 35% increase to about a 40% increase, about a 40%increase to about 10,000% increase, about a 40% increase to about a9,000% increase, about a 40% increase to about a 8,000% increase, abouta 40% increase to about a 7,000% increase, about a 40% increase to abouta 6,000% increase, about a 40% increase to about a 5,000% increase,about a 40% increase to about a 4,000% increase, about a 40% increase toabout a 3,000% increase, about a 40% increase to about a 2,000%increase, about a 40% increase to about a 1,000% increase, about a 40%increase to about a 500% increase, about a 40% increase to about a 450%increase, about a 40% increase to about a 400% increase, about a 40%increase to about a 350% increase, about a 40% increase to about a 300%increase, about a 40% increase to about a 250% increase, about a 40%increase to about a 200% increase, about a 40% increase to about a 180%increase, about a 40% increase to about a 160% increase, about a 40%increase to about a 140% increase, about a 40% increase to about a 120%increase, about a 40% increase to about a 100% increase, about a 40%increase to about a 95% increase, about a 40% increase to about a 90%increase, about a 40% increase to about a 85% increase, about a 40%increase to about a 80% increase, about a 40% increase to about a 75%increase, about a 40% increase to about a 70% increase, about a 40%increase to about a 65% increase, about a 40% increase to about a 60%increase, about a 40% increase to about a 55% increase, about a 40%increase to about a 50% increase, about a 40% increase to about a 45%increase, about a 45% increase to about 10,000% increase, about a 45%increase to about a 9,000% increase, about a 45% increase to about a8,000% increase, about a 45% increase to about a 7,000% increase, abouta 45% increase to about a 6,000% increase, about a 45% increase to abouta 5,000% increase, about a 45% increase to about a 4,000% increase,about a 45% increase to about a 3,000% increase, about a 45% increase toabout a 2,000% increase, about a 45% increase to about a 1,000%increase, about a 45% increase to about a 500% increase, about a 45%increase to about a 450% increase, about a 45% increase to about a 400%increase, about a 45% increase to about a 350% increase, about a 45%increase to about a 300% increase, about a 45% increase to about a 250%increase, about a 45% increase to about a 200% increase, about a 45%increase to about a 180% increase, about a 45% increase to about a 160%increase, about a 45% increase to about a 140% increase, about a 45%increase to about a 120% increase, about a 45% increase to about a 100%increase, about a 45% increase to about a 95% increase, about a 45%increase to about a 90% increase, about a 45% increase to about a 85%increase, about a 45% increase to about a 80% increase, about a 45%increase to about a 75% increase, about a 45% increase to about a 70%increase, about a 45% increase to about a 65% increase, about a 45%increase to about a 60% increase, about a 45% increase to about a 55%increase, about a 45% increase to about a 50% increase, about a 50%increase to about 10,000% increase, about a 50% increase to about a9,000% increase, about a 50% increase to about a 8,000% increase, abouta 50% increase to about a 7,000% increase, about a 50% increase to abouta 6,000% increase, about a 50% increase to about a 5,000% increase,about a 50% increase to about a 4,000% increase, about a 50% increase toabout a 3,000% increase, about a 50% increase to about a 2,000%increase, about a 50% increase to about a 1,000% increase, about a 50%increase to about a 500% increase, about a 50% increase to about a 450%increase, about a 50% increase to about a 400% increase, about a 50%increase to about a 350% increase, about a 50% increase to about a 300%increase, about a 50% increase to about a 250% increase, about a 50%increase to about a 200% increase, about a 50% increase to about a 180%increase, about a 50% increase to about a 160% increase, about a 50%increase to about a 140% increase, about a 50% increase to about a 120%increase, about a 50% increase to about a 100% increase, about a 50%increase to about a 95% increase, about a 50% increase to about a 90%increase, about a 50% increase to about a 85% increase, about a 50%increase to about a 80% increase, about a 50% increase to about a 75%increase, about a 50% increase to about a 70% increase, about a 50%increase to about a 65% increase, about a 50% increase to about a 60%increase, about a 50% increase to about a 55% increase, about a 55%increase to about 10,000% increase, about a 55% increase to about a9,000% increase, about a 55% increase to about a 8,000% increase, abouta 55% increase to about a 7,000% increase, about a 55% increase to abouta 6,000% increase, about a 55% increase to about a 5,000% increase,about a 55% increase to about a 4,000% increase, about a 55% increase toabout a 3,000% increase, about a 55% increase to about a 2,000%increase, about a 55% increase to about a 1,000% increase, about a 55%increase to about a 500% increase, about a 55% increase to about a 450%increase, about a 55% increase to about a 400% increase, about a 55%increase to about a 350% increase, about a 55% increase to about a 300%increase, about a 55% increase to about a 250% increase, about a 55%increase to about a 200% increase, about a 55% increase to about a 180%increase, about a 55% increase to about a 160% increase, about a 55%increase to about a 140% increase, about a 55% increase to about a 120%increase, about a 55% increase to about a 100% increase, about a 55%increase to about a 95% increase, about a 55% increase to about a 90%increase, about a 55% increase to about a 85% increase, about a 55%increase to about a 80% increase, about a 55% increase to about a 75%increase, about a 55% increase to about a 70% increase, about a 55%increase to about a 65% increase, about a 55% increase to about a 60%increase, about a 60% increase to about 10,000% increase, about a 60%increase to about a 9,000% increase, about a 60% increase to about a8,000% increase, about a 60% increase to about a 7,000% increase, abouta 60% increase to about a 6,000% increase, about a 60% increase to abouta 5,000% increase, about a 60% increase to about a 4,000% increase,about a 60% increase to about a 3,000% increase, about a 60% increase toabout a 2,000% increase, about a 60% increase to about a 1,000%increase, about a 60% increase to about a 500% increase, about a 60%increase to about a 450% increase, about a 60% increase to about a 400%increase, about a 60% increase to about a 350% increase, about a 60%increase to about a 300% increase, about a 60% increase to about a 250%increase, about a 60% increase to about a 200% increase, about a 60%increase to about a 180% increase, about a 60% increase to about a 160%increase, about a 60% increase to about a 140% increase, about a 60%increase to about a 120% increase, about a 60% increase to about a 100%increase, about a 60% increase to about a 95% increase, about a 60%increase to about a 90% increase, about a 60% increase to about a 85%increase, about a 60% increase to about a 80% increase, about a 60%increase to about a 75% increase, about a 60% increase to about a 70%increase, about a 60% increase to about a 65% increase, about a 65%increase to about 10,000% increase, about a 65% increase to about a9,000% increase, about a 65% increase to about a 8,000% increase, abouta 65% increase to about a 7,000% increase, about a 65% increase to abouta 6,000% increase, about a 65% increase to about a 5,000% increase,about a 65% increase to about a 4,000% increase, about a 65% increase toabout a 3,000% increase, about a 65% increase to about a 2,000%increase, about a 65% increase to about a 1,000% increase, about a 65%increase to about a 500% increase, about a 65% increase to about a 450%increase, about a 65% increase to about a 400% increase, about a 65%increase to about a 350% increase, about a 65% increase to about a 300%increase, about a 65% increase to about a 250% increase, about a 65%increase to about a 200% increase, about a 65% increase to about a 180%increase, about a 65% increase to about a 160% increase, about a 65%increase to about a 140% increase, about a 65% increase to about a 120%increase, about a 65% increase to about a 100% increase, about a 65%increase to about a 95% increase, about a 65% increase to about a 90%increase, about a 65% increase to about a 85% increase, about a 65%increase to about a 80% increase, about a 65% increase to about a 75%increase, about a 65% increase to about a 70% increase, about a 70%increase to about 10,000% increase, about a 70% increase to about a9,000% increase, about a 70% increase to about a 8,000% increase, abouta 70% increase to about a 7,000% increase, about a 70% increase to abouta 6,000% increase, about a 70% increase to about a 5,000% increase,about a 70% increase to about a 4,000% increase, about a 70% increase toabout a 3,000% increase, about a 70% increase to about a 2,000%increase, about a 70% increase to about a 1,000% increase, about a 70%increase to about a 500% increase, about a 70% increase to about a 450%increase, about a 70% increase to about a 400% increase, about a 70%increase to about a 350% increase, about a 70% increase to about a 300%increase, about a 70% increase to about a 250% increase, about a 70%increase to about a 200% increase, about a 70% increase to about a 180%increase, about a 70% increase to about a 160% increase, about a 70%increase to about a 140% increase, about a 70% increase to about a 120%increase, about a 70% increase to about a 100% increase, about a 70%increase to about a 95% increase, about a 70% increase to about a 90%increase, about a 70% increase to about a 85% increase, about a 70%increase to about a 80% increase, about a 70% increase to about a 75%increase, about a 75% increase to about 10,000% increase, about a 75%increase to about a 9,000% increase, about a 75% increase to about a8,000% increase, about a 75% increase to about a 7,000% increase, abouta 75% increase to about a 6,000% increase, about a 75% increase to abouta 5,000% increase, about a 75% increase to about a 4,000% increase,about a 75% increase to about a 3,000% increase, about a 75% increase toabout a 2,000% increase, about a 75% increase to about a 1,000%increase, about a 75% increase to about a 500% increase, about a 75%increase to about a 450% increase, about a 75% increase to about a 400%increase, about a 75% increase to about a 350% increase, about a 75%increase to about a 300% increase, about a 75% increase to about a 250%increase, about a 75% increase to about a 200% increase, about a 75%increase to about a 180% increase, about a 75% increase to about a 160%increase, about a 75% increase to about a 140% increase, about a 75%increase to about a 120% increase, about a 75% increase to about a 100%increase, about a 75% increase to about a 95% increase, about a 75%increase to about a 90% increase, about a 75% increase to about a 85%increase, about a 75% increase to about a 80%, about a 80% increase toabout 10,000% increase, about a 80% increase to about a 9,000% increase,about a 80% increase to about a 8,000% increase, about a 80% increase toabout a 7,000% increase, about a 80% increase to about a 6,000%increase, about a 80% increase to about a 5,000% increase, about a 80%increase to about a 4,000% increase, about a 80% increase to about a3,000% increase, about a 80% increase to about a 2,000% increase, abouta 80% increase to about a 1,000% increase, increase, about a 80%increase to about a 500% increase, about a 80% increase to about a 450%increase, about a 80% increase to about a 400% increase, about a 80%increase to about a 350% increase, about a 80% increase to about a 300%increase, about a 80% increase to about a 250% increase, about a 80%increase to about a 200% increase, about a 80% increase to about a 180%increase, about a 80% increase to about a 160% increase, about a 80%increase to about a 140% increase, about a 80% increase to about a 120%increase, about a 80% increase to about a 100% increase, about a 80%increase to about a 95% increase, about a 80% increase to about a 90%increase, about a 80% increase to about a 85% increase, about a 85%increase to about 10,000% increase, about a 85% increase to about a9,000% increase, about a 85% increase to about a 8,000% increase, abouta 85% increase to about a 7,000% increase, about a 85% increase to abouta 6,000% increase, about a 85% increase to about a 5,000% increase,about a 85% increase to about a 4,000% increase, about a 85% increase toabout a 3,000% increase, about a 85% increase to about a 2,000%increase, about a 85% increase to about a 1,000% increase, about a 85%increase to about a 500% increase, about a 85% increase to about a 450%increase, about a 85% increase to about a 400% increase, about a 85%increase to about a 350% increase, about a 85% increase to about a 300%increase, about a 85% increase to about a 250% increase, about a 85%increase to about a 200% increase, about a 85% increase to about a 180%increase, about a 85% increase to about a 160% increase, about a 85%increase to about a 140% increase, about a 85% increase to about a 120%increase, about a 85% increase to about a 100% increase, about a 85%increase to about a 95% increase, about a 85% increase to about a 90%increase, about a 90% increase to about 10,000% increase, about a 90%increase to about a 9,000% increase, about a 90% increase to about a8,000% increase, about a 90% increase to about a 7,000% increase, abouta 90% increase to about a 6,000% increase, about a 90% increase to abouta 5,000% increase, about a 90% increase to about a 4,000% increase,about a 90% increase to about a 3,000% increase, about a 90% increase toabout a 2,000% increase, about a 90% increase to about a 1,000%increase, about a 90% increase to about a 500% increase, about a 90%increase to about a 450% increase, about a 90% increase to about a 400%increase, about a 90% increase to about a 350% increase, about a 90%increase to about a 300% increase, about a 90% increase to about a 250%increase, about a 90% increase to about a 200% increase, about a 90%increase to about a 180% increase, about a 90% increase to about a 160%increase, about a 90% increase to about a 140% increase, about a 90%increase to about a 120% increase, about a 90% increase to about a 100%increase, about a 90% increase to about a 95% increase, about a 95%increase to about 10,000% increase, about a 95% increase to about a9,000% increase, about a 95% increase to about a 8,000% increase, abouta 95% increase to about a 7,000% increase, about a 95% increase to abouta 6,000% increase, about a 95% increase to about a 5,000% increase,about a 95% increase to about a 4,000% increase, about a 95% increase toabout a 3,000% increase, about a 95% increase to about a 2,000%increase, about a 95% increase to about a 1,000% increase, about a 95%increase to about a 500% increase, about a 95% increase to about a 450%increase, about a 95% increase to about a 400% increase, about a 95%increase to about a 350% increase, about a 95% increase to about a 300%increase, about a 95% increase to about a 250% increase, about a 95%increase to about a 200% increase, about a 95% increase to about a 180%increase, about a 95% increase to about a 160% increase, about a 95%increase to about a 140% increase, about a 95% increase to about a 120%increase, about a 95% increase to about a 100% increase, about a 100%increase to about 10,000% increase, about a 100% increase to about a9,000% increase, about a 100% increase to about a 8,000% increase, abouta 100% increase to about a 7,000% increase, about a 100% increase toabout a 6,000% increase, about a 100% increase to about a 5,000%increase, about a 100% increase to about a 4,000% increase, about a 100%increase to about a 3,000% increase, about a 100% increase to about a2,000% increase, about a 100% increase to about a 1,000% increase, abouta 100% increase to about a 500% increase, about a 100% increase to abouta 450% increase, about a 100% increase to about a 400% increase, about a100% increase to about a 350% increase, about a 100% increase to about a300% increase, about a 100% increase to about a 250% increase, about a100% increase to about a 200% increase, about a 100% increase to about a180% increase, about a 100% increase to about a 160% increase, about a100% increase to about a 140% increase, about a 100% increase to about a120% increase, about a 120% increase to about 10,000% increase, about a120% increase to about a 9,000% increase, about a 120% increase to abouta 8,000% increase, about a 120% increase to about a 7,000% increase,about a 120% increase to about a 6,000% increase, about a 120% increaseto about a 5,000% increase, about a 120% increase to about a 4,000%increase, about a 120% increase to about a 3,000% increase, about a 120%increase to about a 2,000% increase, about a 120% increase to about a1,000% increase, about a 120% increase to about a 500% increase, about a120% increase to about a 450% increase, about a 120% increase to about a400% increase, about a 120% increase to about a 350% increase, about a120% increase to about a 300% increase, about a 120% increase to about a250% increase, about a 120% increase to about a 200% increase, about a120% increase to about a 180% increase, about a 120% increase to about a160% increase, about a 120% increase to about a 140% increase, about a140% increase to about 10,000% increase, about a 140% increase to abouta 9,000% increase, about a 140% increase to about a 8,000% increase,about a 140% increase to about a 7,000% increase, about a 140% increaseto about a 6,000% increase, about a 140% increase to about a 5,000%increase, about a 140% increase to about a 4,000% increase, about a 140%increase to about a 3,000% increase, about a 140% increase to about a2,000% increase, about a 140% increase to about a 1,000% increase, abouta 140% increase to about a 500% increase, about a 140% increase to abouta 450% increase, about a 140% increase to about a 400% increase, about a140% increase to about a 350% increase, about a 140% increase to about a300% increase, about a 140% increase to about a 250% increase, about a140% increase to about a 200% increase, about a 140% increase to about a180% increase, about a 140% increase to about a 160% increase, about a160% increase to about 10,000% increase, about a 160% increase to abouta 9,000% increase, about a 160% increase to about a 8,000% increase,about a 160% increase to about a 7,000% increase, about a 160% increaseto about a 6,000% increase, about a 160% increase to about a 5,000%increase, about a 160% increase to about a 4,000% increase, about a 160%increase to about a 3,000% increase, about a 160% increase to about a2,000% increase, about a 160% increase to about a 1,000% increase, abouta 160% increase to about a 500% increase, about a 160% increase to abouta 450% increase, about a 160% increase to about a 400% increase, about a160% increase to about a 350% increase, about a 160% increase to about a300% increase, about a 160% increase to about a 250% increase, about a160% increase to about a 200% increase, about a 160% increase to about a180% increase, about a 180% increase to about 10,000% increase, about a180% increase to about a 9,000% increase, about a 180% increase to abouta 8,000% increase, about a 180% increase to about a 7,000% increase,about a 180% increase to about a 6,000% increase, about a 180% increaseto about a 5,000% increase, about a 180% increase to about a 4,000%increase, about a 180% increase to about a 3,000% increase, about a 180%increase to about a 2,000% increase, about a 180% increase to about a1,000% increase, about a 180% increase to about a 500% increase, about a180% increase to about a 450% increase, about a 180% increase to about a400% increase, about a 180% increase to about a 350% increase, about a180% increase to about a 300% increase, about a 180% increase to about a250% increase, about a 180% increase to about a 200% increase, about a200% increase to about 10,000% increase, about a 200% increase to abouta 9,000% increase, about a 200% increase to about a 8,000% increase,about a 200% increase to about a 7,000% increase, about a 200% increaseto about a 6,000% increase, about a 200% increase to about a 5,000%increase, about a 200% increase to about a 4,000% increase, about a 200%increase to about a 3,000% increase, about a 200% increase to about a2,000% increase, about a 200% increase to about a 1,000% increase, abouta 200% increase to about a 500% increase, about a 200% increase to abouta 450% increase, about a 200% increase to about a 400% increase, about a200% increase to about a 350% increase, about a 200% increase to about a300% increase, about a 200% increase to about a 250% increase, about a250% increase to about 10,000% increase, about a 250% increase to abouta 9,000% increase, about a 250% increase to about a 8,000% increase,about a 250% increase to about a 7,000% increase, about a 250% increaseto about a 6,000% increase, about a 250% increase to about a 5,000%increase, about a 250% increase to about a 4,000% increase, about a 250%increase to about a 3,000% increase, about a 250% increase to about a2,000% increase, about a 250% increase to about a 1,000% increase, abouta 250% increase to about a 500% increase, about a 250% increase to abouta 450% increase, about a 250% increase to about a 400% increase, about a250% increase to about a 350% increase, about a 250% increase to about a300% increase, about a 300% increase to about 10,000% increase, about a300% increase to about a 9,000% increase, about a 300% increase to abouta 8,000% increase, about a 300% increase to about a 7,000% increase,about a 300% increase to about a 6,000% increase, about a 300% increaseto about a 5,000% increase, about a 300% increase to about a 4,000%increase, about a 300% increase to about a 3,000% increase, about a 300%increase to about a 2,000% increase, about a 300% increase to about a1,000% increase, about a 300% increase to about a 500% increase, about a300% increase to about a 450% increase, about a 300% increase to about a400% increase, about a 300% increase to about a 350% increase, about a350% increase to about 10,000% increase, about a 350% increase to abouta 9,000% increase, about a 350% increase to about a 8,000% increase,about a 350% increase to about a 7,000% increase, about a 350% increaseto about a 6,000% increase, about a 350% increase to about a 5,000%increase, about a 350% increase to about a 4,000% increase, about a 350%increase to about a 3,000% increase, about a 350% increase to about a2,000% increase, about a 350% increase to about a 1,000% increase, abouta 350% increase to about a 500% increase, about a 350% increase to abouta 450% increase, about a 350% increase to about a 400% increase, about a400% increase to about 10,000% increase, about a 400% increase to abouta 9.000% increase, about a 400% increase to about a 8,000% increase,about a 400% increase to about a 7,000% increase, about a 400% increaseto about a 6,000% increase, about a 400% increase to about a 5,000%increase, about a 400% increase to about a 4,000% increase, about a 400%increase to about a 3,000% increase, about a 400% increase to about a2,000% increase, about a 400% increase to about a 1,000% increase, abouta 400% increase to about a 500% increase, about a 400% increase to abouta 450% increase, about a 450% increase to about 10,000% increase, abouta 450% increase to about a 9,000% increase, about a 450% increase toabout a 8,000% increase, about a 450% increase to about a 7,000%increase, about a 450% increase to about a 6,000% increase, about a 450%increase to about a 5,000% increase, about a 450% increase to about a4,000% increase, about a 450% increase to about a 3.000% increase, abouta 450% increase to about a 2,000% increase, about a 450% increase toabout a 1,000% increase, about a 450% increase to about a 500% increase,about a 500% increase to about 10,000% increase, about a 500% increaseto about a 9,000% increase, about a 500% increase to about a 8,000%increase, about a 500% increase to about a 7,000% increase, about a 500%increase to about a 6,000% increase, about a 500% increase to about a5,000% increase, about a 500% increase to about a 4,000% increase, abouta 500% increase to about a 3,000% increase, about a 500% increase toabout a 2,000% increase, about a 500% increase to about a 1,000%increase, about a 1,000% increase to about 10,000% increase, about a1,000% increase to about a 9,000% increase, about a 1,000% increase toabout a 8,000% increase, about a 1,000% increase to about a 7,000%increase, about a 1,000% increase to about a 6,000% increase, about a1,000% increase to about a 5,000% increase, about a 1,000% increase toabout a 4,000% increase, about a 1,000% increase to about a 3,000%increase, about a 1,000% increase to about a 2,000% increase, about a2,000% increase to about 10,000% increase, about a 2,000% increase toabout a 9,000% increase, about a 2,000% increase to about a 8,000%increase, about a 2,000% increase to about a 7,000% increase, about a2,000% increase to about a 6,000% increase, about a 2,000% increase toabout a 5,000% increase, about a 2,000% increase to about a 4,000%increase, about a 2,000% increase to about a 3,000% increase, about a3,000% increase to about 10,000% increase, about a 3,000% increase toabout a 9,000% increase, about a 3,000% increase to about a 8,000%increase, about a 3,000% increase to about a 7,000% increase, about a3,000% increase to about a 6,000% increase, about a 3,000% increase toabout a 5,000% increase, about a 3,000% increase to about a 4,000%increase, about a 4,000% increase to about 10,000% increase, about a4,000% increase to about a 9,000% increase, about a 4,000% increase toabout a 8,000% increase, about a 4,000% increase to about a 7,000%increase, about a 4,000% increase to about a 6,000% increase, about a4,000% increase to about a 5,000% increase, about a 5,000% increase toabout 10,000% increase, about a 5,000% increase to about a 9,000%increase, about a 5,000% increase to about a 8,000% increase, about a5,000% increase to about a 7,000% increase, about a 5,000% increase toabout a 6,000% increase, about a 6,000% increase to about 10,000%increase, about a 6,000% increase to about a 9,000% increase, about a6,000% increase to about a 8,000% increase, about a 6,000% increase toabout a 7,000% increase, about a 7,000% increase to about 10,000%increase, about a 7,000% increase to about a 9,000% increase, about a7,000% increase to about a 8,000% increase, about a 8,000% increase toabout 10,000% increase, about a 8,000% increase to about a 9,000%increase, or about a 9,000% increase to about 10,000%) in toxinliberation in the target mammalian cell (e.g., any of the targetmammalian cells described herein) as compared to a composition includingthe same amount of a control ABPC (e.g., any of the exemplary controlABPCs described herein).

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 0.1-foldincrease, at least a 0.2-fold increase, at least a 0.3-fold increase, atleast a 0.4-fold increase, at least a 0.5-fold increase, at least a0.6-fold increase, at least a 0.7-fold increase, at least a 0.8-foldincrease, at least a 0.9-fold increase, at least a 1.0-fold increase, atleast a 1.2-fold increase, at least a 1.4-fold increase, at least a1.5-fold increase, at least a 1.6-fold increase, at least a 1.8-foldincrease, at least a 2.0-fold increase, at least a 2.2-fold increase, atleast a 2.4-fold increase, at least a 2.5-fold increase, at least a2.6-fold increase, at least a 2.8-fold increase, at least a 3.0-foldincrease, at least a 3.5-fold increase, at least a 4.0-fold increase, atleast a 4.5-fold increase, at least a 5.0-fold increase, at least a5.5-fold increase, at least a 6.0-fold increase, at least a 6.5-foldincrease, at least a 7.0-fold increase, at least a 7.5-fold increase, atleast a 8.0-fold increase, at least a 8.5-fold increase, at least a9.0-fold increase, at least a 9.5-fold increase, at least a 10-foldincrease, at least a 15-fold increase, at least a 20-fold increase, atleast a 25-fold increase, at least a 30-fold increase, at least a35-fold increase, at least a 40-fold increase, at least a 45-foldincrease, at least a 50-fold increase, at least a 55-fold increase, atleast a 60-fold increase, at least a 65-fold increase, at least a70-fold increase, at least a 75-fold increase, at least a 80-foldincrease, at least a 85-fold increase, at least a 90-fold increase, atleast a 95-fold increase, or at least a 100-fold increase, or about a0.1-fold increase to about a 100-fold increase, about 0.1-fold increaseto about a 90-fold increase, about 0.1-fold increase to about a 80-foldincrease, about a 0.1-fold increase to about a 70-fold increase, about a0.1-fold increase to about a 60-fold increase, about a 0.1-fold increaseto about a 50-fold increase, about a 0.1-fold increase to about a40-fold increase, about a 0.1-fold increase to about a 30-fold increase,about 0.1-fold increase to about 20-fold increase, about a 0.1-foldincrease to about a 10-fold increase, about a 0.1-fold increase to abouta 9.5-fold increase, about a 0.1-fold increase to about a 9.0-foldincrease, about a 0.1-fold increase to about a 8.5-fold increase, abouta 0.1-fold increase to about a 8.0-fold increase, about a 0.1-foldincrease to about a 7.5-fold increase, about a 0.1-fold increase toabout a 7.0-fold increase, about a 0.1-fold increase to about a 6.5-foldincrease, about a 0.1-fold increase to about a 6.0-fold increase, abouta 0.1-fold increase to about a 5.5-fold increase, about a 0.1-foldincrease to about a 5.0-fold increase, about a 0.1-fold increase toabout a 4.5-fold increase, about a 0.1-fold increase to about a 4.0-foldincrease, about a 0.1-fold increase to about a 3.5-fold increase, about0.1-fold increase to about a 3.0-fold increase, about a 0.1-foldincrease to about a 2.8-fold increase, about a 0.1-fold increase toabout a 2.6-fold increase, about a 0.1-fold increase to about a 2.5-foldincrease, about a 0.1-fold increase to about a 2.4-fold increase, abouta 0.1-fold increase to about a 2.2-fold increase, about a 0.1-foldincrease to about a 2.0-fold increase, about a 0.1-fold increase toabout a 1.8-fold increase, about a 0.1-fold increase to about a 1.6-foldincrease, about a 0.1-fold increase to about a 1.5-fold increase, abouta 0.1-fold increase to about a 1.4-fold increase, about a 0.1-foldincrease to about a 1.2-fold increase, about a 0.1-fold increase toabout a 1.0-fold increase, about a 0.1-fold increase to about a 0.9-foldincrease, about a 0.1-fold increase to about a 0.8-fold increase, abouta 0.1-fold increase to about a 0.7-fold increase, about a 0.1-foldincrease to about a 0.6-fold increase, about a 0.1-fold increase toabout a 0.5-fold increase, about a 0.1-fold increase to about a 0.4-foldincrease, about a 0.1-fold increase to about a 0.3-fold increase, abouta 0.2-fold increase to about a 100-fold increase, about 0.2-foldincrease to about a 90-fold increase, about 0.2-fold increase to about a80-fold increase, about a 0.2-fold increase to about a 70-fold increase,about a 0.2-fold increase to about a 60-fold increase, about a 0.2-foldincrease to about a 50-fold increase, about a 0.2-fold increase to abouta 40-fold increase, about a 0.2-fold increase to about a 30-foldincrease, about 0.2-fold increase to about 20-fold increase, about a0.2-fold increase to about a 10-fold increase, about a 0.2-fold increaseto about a 9.5-fold increase, about a 0.2-fold increase to about a9.0-fold increase, about a 0.2-fold increase to about a 8.5-foldincrease, about a 0.2-fold increase to about a 8.0-fold increase, abouta 0.2-fold increase to about a 7.5-fold increase, about a 0.2-foldincrease to about a 7.0-fold increase, about a 0.2-fold increase toabout a 6.5-fold increase, about a 0.2-fold increase to about a 6.0-foldincrease, about a 0.2-fold increase to about a 5.5-fold increase, abouta 0.2-fold increase to about a 5.0-fold increase, about a 0.2-foldincrease to about a 4.5-fold increase, about a 0.2-fold increase toabout a 4.0-fold increase, about a 0.2-fold increase to about a 3.5-foldincrease, about 0.2-fold increase to about a 3.0-fold increase, about a0.2-fold increase to about a 2.8-fold increase, about a 0.2-foldincrease to about a 2.6-fold increase, about a 0.2-fold increase toabout a 2.5-fold increase, about a 0.2-fold increase to about a 2.4-foldincrease, about a 0.2-fold increase to about a 2.2-fold increase, abouta 0.2-fold increase to about a 2.0-fold increase, about a 0.2-foldincrease to about a 1.8-fold increase, about a 0.2-fold increase toabout a 1.6-fold increase, about a 0.2-fold increase to about a 1.5-foldincrease, about a 0.2-fold increase to about a 1.4-fold increase, abouta 0.2-fold increase to about a 1.2-fold increase, about a 0.2-foldincrease to about a 1.0-fold increase, about a 0.2-fold increase toabout a 0.9-fold increase, about a 0.2-fold increase to about a 0.8-foldincrease, about a 0.2-fold increase to about a 0.7-fold increase, abouta 0.2-fold increase to about a 0.6-fold increase, about a 0.2-foldincrease to about a 0.5-fold increase, about a 0.2-fold increase toabout a 0.4-fold increase, about a 0.3-fold increase to about a 100-foldincrease, about 0.3-fold increase to about a 90-fold increase, about0.3-fold increase to about a 80-fold increase, about a 0.3-fold increaseto about a 70-fold increase, about a 0.3-fold increase to about a60-fold increase, about a 0.3-fold increase to about a 50-fold increase,about a 0.3-fold increase to about a 40-fold increase, about a 0.3-foldincrease to about a 30-fold increase, about 0.3-fold increase to about20-fold increase, about a 0.3-fold increase to about a 10-fold increase,about a 0.3-fold increase to about a 9.5-fold increase, about a 0.3-foldincrease to about a 9.0-fold increase, about a 0.3-fold increase toabout a 8.5-fold increase, about a 0.3-fold increase to about a 8.0-foldincrease, about a 0.3-fold increase to about a 7.5-fold increase, abouta 0.3-fold increase to about a 7.0-fold increase, about a 0.3-foldincrease to about a 6.5-fold increase, about a 0.3-fold increase toabout a 6.0-fold increase, about a 0.3-fold increase to about a 5.5-foldincrease, about a 0.3-fold increase to about a 5.0-fold increase, abouta 0.3-fold increase to about a 4.5-fold increase, about a 0.3-foldincrease to about a 4.0-fold increase, about a 0.3-fold increase toabout a 3.5-fold increase, about 0.3-fold increase to about a 3.0-foldincrease, about a 0.3-fold increase to about a 2.8-fold increase, abouta 0.3-fold increase to about a 2.6-fold increase, about a 0.3-foldincrease to about a 2.5-fold increase, about a 0.3-fold increase toabout a 2.4-fold increase, about a 0.3-fold increase to about a 2.2-foldincrease, about a 0.3-fold increase to about a 2.0-fold increase, abouta 0.3-fold increase to about a 1.8-fold increase, about a 0.3-foldincrease to about a 1.6-fold increase, about a 0.3-fold increase toabout a 1.5-fold increase, about a 0.3-fold increase to about a 1.4-foldincrease, about a 0.3-fold increase to about a 1.2-fold increase, abouta 0.3-fold increase to about a 1.0-fold increase, about a 0.3-foldincrease to about a 0.9-fold increase, about a 0.3-fold increase toabout a 0.8-fold increase, about a 0.3-fold increase to about a 0.7-foldincrease, about a 0.3-fold increase to about a 0.6-fold increase, abouta 0.3-fold increase to about a 0.5-fold increase, about a 0.4-foldincrease to about a 100-fold increase, about 0.4-fold increase to abouta 90-fold increase, about 0.4-fold increase to about a 80-fold increase,about a 0.4-fold increase to about a 70-fold increase, about a 0.4-foldincrease to about a 60-fold increase, about a 0.4-fold increase to abouta 50-fold increase, about a 0.4-fold increase to about a 40-foldincrease, about a 0.4-fold increase to about a 30-fold increase, about0.4-fold increase to about 20-fold increase, about a 0.4-fold increaseto about a 10-fold increase, about a 0.4-fold increase to about a9.5-fold increase, about a 0.4-fold increase to about a 9.0-foldincrease, about a 0.4-fold increase to about a 8.5-fold increase, abouta 0.4-fold increase to about a 8.0-fold increase, about a 0.4-foldincrease to about a 7.5-fold increase, about a 0.4-fold increase toabout a 7.0-fold increase, about a 0.4-fold increase to about a 6.5-foldincrease, about a 0.4-fold increase to about a 6.0-fold increase, abouta 0.4-fold increase to about a 5.5-fold increase, about a 0.4-foldincrease to about a 5.0-fold increase, about a 0.4-fold increase toabout a 4.5-fold increase, about a 0.4-fold increase to about a 4.0-foldincrease, about a 0.4-fold increase to about a 3.5-fold increase, about0.4-fold increase to about a 3.0-fold increase, about a 0.4-foldincrease to about a 2.8-fold increase, about a 0.4-fold increase toabout a 2.6-fold increase, about a 0.4-fold increase to about a 2.5-foldincrease, about a 0.4-fold increase to about a 2.4-fold increase, abouta 0.4-fold increase to about a 2.2-fold increase, about a 0.4-foldincrease to about a 2.0-fold increase, about a 0.4-fold increase toabout a 1.8-fold increase, about a 0.4-fold increase to about a 1.6-foldincrease, about a 0.4-fold increase to about a 1.5-fold increase, abouta 0.4-fold increase to about a 1.4-fold increase, about a 0.4-foldincrease to about a 1.2-fold increase, about a 0.4-fold increase toabout a 1.0-fold increase, about a 0.4-fold increase to about a 0.9-foldincrease, about a 0.4-fold increase to about a 0.8-fold increase, abouta 0.4-fold increase to about a 0.7-fold increase, about a 0.4-foldincrease to about a 0.6-fold increase, about a 0.5-fold increase toabout a 100-fold increase, about 0.5-fold increase to about a 90-foldincrease, about 0.5-fold increase to about a 80-fold increase, about a0.5-fold increase to about a 70-fold increase, about a 0.5-fold increaseto about a 60-fold increase, about a 0.5-fold increase to about a50-fold increase, about a 0.5-fold increase to about a 40-fold increase,about a 0.5-fold increase to about a 30-fold increase, about 0.5-foldincrease to about 20-fold increase, about a 0.5-fold increase to about a10-fold increase, about a 0.5-fold increase to about a 9.5-foldincrease, about a 0.5-fold increase to about a 9.0-fold increase, abouta 0.5-fold increase to about a 8.5-fold increase, about a 0.5-foldincrease to about a 8.0-fold increase, about a 0.5-fold increase toabout a 7.5-fold increase, about a 0.5-fold increase to about a 7.0-foldincrease, about a 0.5-fold increase to about a 6.5-fold increase, abouta 0.5-fold increase to about a 6.0-fold increase, about a 0.5-foldincrease to about a 5.5-fold increase, about a 0.5-fold increase toabout a 5.0-fold increase, about a 0.5-fold increase to about a 4.5-foldincrease, about a 0.5-fold increase to about a 4.0-fold increase, abouta 0.5-fold increase to about a 3.5-fold increase, about 0.5-foldincrease to about a 3.0-fold increase, about a 0.5-fold increase toabout a 2.8-fold increase, about a 0.5-fold increase to about a 2.6-foldincrease, about a 0.5-fold increase to about a 2.5-fold increase, abouta 0.5-fold increase to about a 2.4-fold increase, about a 0.5-foldincrease to about a 2.2-fold increase, about a 0.5-fold increase toabout a 2.0-fold increase, about a 0.5-fold increase to about a 1.8-foldincrease, about a 0.5-fold increase to about a 1.6-fold increase, abouta 0.5-fold increase to about a 1.5-fold increase, about a 0.5-foldincrease to about a 1.4-fold increase, about a 0.5-fold increase toabout a 1.2-fold increase, about a 0.5-fold increase to about a 1.0-foldincrease, about a 0.5-fold increase to about a 0.9-fold increase, abouta 0.5-fold increase to about a 0.8-fold increase, about a 0.5-foldincrease to about a 0.7-fold increase, about a 0.6-fold increase toabout a 100-fold increase, about 0.6-fold increase to about a 90-foldincrease, about 0.6-fold increase to about a 80-fold increase, about a0.6-fold increase to about a 70-fold increase, about a 0.6-fold increaseto about a 60-fold increase, about a 0.6-fold increase to about a50-fold increase, about a 0.6-fold increase to about a 40-fold increase,about a 0.6-fold increase to about a 30-fold increase, about 0.6-foldincrease to about 20-fold increase, about a 0.6-fold increase to about a10-fold increase, about a 0.6-fold increase to about a 9.5-foldincrease, about a 0.6-fold increase to about a 9.0-fold increase, abouta 0.6-fold increase to about a 8.5-fold increase, about a 0.6-foldincrease to about a 8.0-fold increase, about a 0.6-fold increase toabout a 7.5-fold increase, about a 0.6-fold increase to about a 7.0-foldincrease, about a 0.6-fold increase to about a 6.5-fold increase, abouta 0.6-fold increase to about a 6.0-fold increase, about a 0.6-foldincrease to about a 5.5-fold increase, about a 0.6-fold increase toabout a 5.0-fold increase, about a 0.6-fold increase to about a 4.5-foldincrease, about a 0.6-fold increase to about a 4.0-fold increase, abouta 0.6-fold increase to about a 3.5-fold increase, about 0.6-foldincrease to about a 3.0-fold increase, about a 0.6-fold increase toabout a 2.8-fold increase, about a 0.6-fold increase to about a 2.6-foldincrease, about a 0.6-fold increase to about a 2.5-fold increase, abouta 0.6-fold increase to about a 2.4-fold increase, about a 0.6-foldincrease to about a 2.2-fold increase, about a 0.6-fold increase toabout a 2.0-fold increase, about a 0.6-fold increase to about a 1.8-foldincrease, about a 0.6-fold increase to about a 1.6-fold increase, abouta 0.6-fold increase to about a 1.5-fold increase, about a 0.6-foldincrease to about a 1.4-fold increase, about a 0.6-fold increase toabout a 1.2-fold increase, about a 0.6-fold increase to about a 1.0-foldincrease, about a 0.6-fold increase to about a 0.9-fold increase, abouta 0.6-fold increase to about a 0.8-fold increase, about a 0.7-foldincrease to about a 100-fold increase, about 0.7-fold increase to abouta 90-fold increase, about 0.7-fold increase to about a 80-fold increase,about a 0.7-fold increase to about a 70-fold increase, about a 0.7-foldincrease to about a 60-fold increase, about a 0.7-fold increase to abouta 50-fold increase, about a 0.7-fold increase to about a 40-foldincrease, about a 0.7-fold increase to about a 30-fold increase, about0.7-fold increase to about 20-fold increase, about a 0.7-fold increaseto about a 10-fold increase, about a 0.7-fold increase to about a9.5-fold increase, about a 0.7-fold increase to about a 9.0-foldincrease, about a 0.7-fold increase to about a 8.5-fold increase, abouta 0.7-fold increase to about a 8.0-fold increase, about a 0.7-foldincrease to about a 7.5-fold increase, about a 0.7-fold increase toabout a 7.0-fold increase, about a 0.7-fold increase to about a 6.5-foldincrease, about a 0.7-fold increase to about a 6.0-fold increase, abouta 0.7-fold increase to about a 5.5-fold increase, about a 0.7-foldincrease to about a 5.0-fold increase, about a 0.7-fold increase toabout a 4.5-fold increase, about a 0.7-fold increase to about a 4.0-foldincrease, about a 0.7-fold increase to about a 3.5-fold increase, about0.7-fold increase to about a 3.0-fold increase, about a 0.7-foldincrease to about a 2.8-fold increase, about a 0.7-fold increase toabout a 2.6-fold increase, about a 0.7-fold increase to about a 2.5-foldincrease, about a 0.7-fold increase to about a 2.4-fold increase, abouta 0.7-fold increase to about a 2.2-fold increase, about a 0.7-foldincrease to about a 2.0-fold increase, about a 0.7-fold increase toabout a 1.8-fold increase, about a 0.7-fold increase to about a 1.6-foldincrease, about a 0.7-fold increase to about a 1.5-fold increase, abouta 0.7-fold increase to about a 1.4-fold increase, about a 0.7-foldincrease to about a 1.2-fold increase, about a 0.7-fold increase toabout a 1.0-fold increase, about a 0.7-fold increase to about a 0.9-foldincrease, about a 0.8-fold increase to about a 100-fold increase, about0.8-fold increase to about a 90-fold increase, about 0.8-fold increaseto about a 80-fold increase, about a 0.8-fold increase to about a70-fold increase, about a 0.8-fold increase to about a 60-fold increase,about a 0.8-fold increase to about a 50-fold increase, about a 0.8-foldincrease to about a 40-fold increase, about a 0.8-fold increase to abouta 30-fold increase, about 0.8-fold increase to about 20-fold increase,about a 0.8-fold increase to about a 10-fold increase, about a 0.8-foldincrease to about a 9.5-fold increase, about a 0.8-fold increase toabout a 9.0-fold increase, about a 0.8-fold increase to about a 8.5-foldincrease, about a 0.8-fold increase to about a 8.0-fold increase, abouta 0.8-fold increase to about a 7.5-fold increase, about a 0.8-foldincrease to about a 7.0-fold increase, about a 0.8-fold increase toabout a 6.5-fold increase, about a 0.8-fold increase to about a 6.0-foldincrease, about a 0.8-fold increase to about a 5.5-fold increase, abouta 0.8-fold increase to about a 5.0-fold increase, about a 0.8-foldincrease to about a 4.5-fold increase, about a 0.8-fold increase toabout a 4.0-fold increase, about a 0.8-fold increase to about a 3.5-foldincrease, about 0.8-fold increase to about a 3.0-fold increase, about a0.8-fold increase to about a 2.8-fold increase, about a 0.8-foldincrease to about a 2.6-fold increase, about a 0.8-fold increase toabout a 2.5-fold increase, about a 0.8-fold increase to about a 2.4-foldincrease, about a 0.8-fold increase to about a 2.2-fold increase, abouta 0.8-fold increase to about a 2.0-fold increase, about a 0.8-foldincrease to about a 1.8-fold increase, about a 0.8-fold increase toabout a 1.6-fold increase, about a 0.8-fold increase to about a 1.5-foldincrease, about a 0.8-fold increase to about a 1.4-fold increase, abouta 0.8-fold increase to about a 1.2-fold increase, about a 0.8-foldincrease to about a 1.0-fold increase, about a 1.0-fold increase toabout a 100-fold increase, about 1.0-fold increase to about a 90-foldincrease, about 1.0-fold increase to about a 80-fold increase, about a1.0-fold increase to about a 70-fold increase, about a 1.0-fold increaseto about a 60-fold increase, about a 1.0-fold increase to about a50-fold increase, about a 1.0-fold increase to about a 40-fold increase,about a 1.0-fold increase to about a 30-fold increase, about 1.0-foldincrease to about 20-fold increase, about a 1.0-fold increase to about a10-fold increase, about a 1.0-fold increase to about a 9.5-foldincrease, about a 1.0-fold increase to about a 9.0-fold increase, abouta 1.0-fold increase to about a 8.5-fold increase, about a 1.0-foldincrease to about a 8.0-fold increase, about a 1.0-fold increase toabout a 7.5-fold increase, about a 1.0-fold increase to about a 7.0-foldincrease, about a 1.0-fold increase to about a 6.5-fold increase, abouta 1.0-fold increase to about a 6.0-fold increase, about a 1.0-foldincrease to about a 5.5-fold increase, about a 1.0-fold increase toabout a 5.0-fold increase, about a 1.0-fold increase to about a 4.5-foldincrease, about a 1.0-fold increase to about a 4.0-fold increase, abouta 1.0-fold increase to about a 3.5-fold increase, about 1.0-foldincrease to about a 3.0-fold increase, about a 1.0-fold increase toabout a 2.8-fold increase, about a 1.0-fold increase to about a 2.6-foldincrease, about a 1.0-fold increase to about a 2.5-fold increase, abouta 1.0-fold increase to about a 2.4-fold increase, about a 1.0-foldincrease to about a 2.2-fold increase, about a 1.0-fold increase toabout a 2.0-fold increase, about a 1.0-fold increase to about a 1.8-foldincrease, about a 1.0-fold increase to about a 1.6-fold increase, abouta 1.0-fold increase to about a 1.5-fold increase, about a 1.0-foldincrease to about a 1.4-fold increase, about a 1.0-fold increase toabout a 1.2-fold increase, about a 1.2-fold increase to about a 100-foldincrease, about 1.2-fold increase to about a 90-fold increase, about1.2-fold increase to about a 80-fold increase, about a 1.2-fold increaseto about a 70-fold increase, about a 1.2-fold increase to about a60-fold increase, about a 1.2-fold increase to about a 50-fold increase,about a 1.2-fold increase to about a 40-fold increase, about a 1.2-foldincrease to about a 30-fold increase, about 1.2-fold increase to about20-fold increase, about a 1.2-fold increase to about a 10-fold increase,about a 1.2-fold increase to about a 9.5-fold increase, about a 1.2-foldincrease to about a 9.0-fold increase, about a 1.2-fold increase toabout a 8.5-fold increase, about a 1.2-fold increase to about a 8.0-foldincrease, about a 1.2-fold increase to about a 7.5-fold increase, abouta 1.2-fold increase to about a 7.0-fold increase, about a 1.2-foldincrease to about a 6.5-fold increase, about a 1.2-fold increase toabout a 6.0-fold increase, about a 1.2-fold increase to about a 5.5-foldincrease, about a 1.2-fold increase to about a 5.0-fold increase, abouta 1.2-fold increase to about a 4.5-fold increase, about a 1.2-foldincrease to about a 4.0-fold increase, about a 1.2-fold increase toabout a 3.5-fold increase, about 1.2-fold increase to about a 3.0-foldincrease, about a 1.2-fold increase to about a 2.8-fold increase, abouta 1.2-fold increase to about a 2.6-fold increase, about a 1.2-foldincrease to about a 2.5-fold increase, about a 1.2-fold increase toabout a 2.4-fold increase, about a 1.2-fold increase to about a 2.2-foldincrease, about a 1.2-fold increase to about a 2.0-fold increase, abouta 1.2-fold increase to about a 1.8-fold increase, about a 1.2-foldincrease to about a 1.6-fold increase, about a 1.2-fold increase toabout a 1.5-fold increase, about a 1.2-fold increase to about a 1.4-foldincrease, about a 1.4-fold increase to about a 100-fold increase, about1.4-fold increase to about a 90-fold increase, about 1.4-fold increaseto about a 80-fold increase, about a 1.4-fold increase to about a70-fold increase, about a 1.4-fold increase to about a 60-fold increase,about a 1.4-fold increase to about a 50-fold increase, about a 1.4-foldincrease to about a 40-fold increase, about a 1.4-fold increase to abouta 30-fold increase, about 1.4-fold increase to about 20-fold increase,about a 1.4-fold increase to about a 10-fold increase, about a 1.4-foldincrease to about a 9.5-fold increase, about a 1.4-fold increase toabout a 9.0-fold increase, about a 1.4-fold increase to about a 8.5-foldincrease, about a 1.4-fold increase to about a 8.0-fold increase, abouta 1.4-fold increase to about a 7.5-fold increase, about a 1.4-foldincrease to about a 7.0-fold increase, about a 1.4-fold increase toabout a 6.5-fold increase, about a 1.4-fold increase to about a 6.0-foldincrease, about a 1.4-fold increase to about a 5.5-fold increase, abouta 1.4-fold increase to about a 5.0-fold increase, about a 1.4-foldincrease to about a 4.5-fold increase, about a 1.4-fold increase toabout a 4.0-fold increase, about a 1.4-fold increase to about a 3.5-foldincrease, about 1.4-fold increase to about a 3.0-fold increase, about a1.4-fold increase to about a 2.8-fold increase, about a 1.4-foldincrease to about a 2.6-fold increase, about a 1.4-fold increase toabout a 2.5-fold increase, about a 1.4-fold increase to about a 2.4-foldincrease, about a 1.4-fold increase to about a 2.2-fold increase, abouta 1.4-fold increase to about a 2.0-fold increase, about a 1.4-foldincrease to about a 1.8-fold increase, about a 1.4-fold increase toabout a 1.6-fold increase, about a 1.6-fold increase to about a 10-foldincrease, about a 1.6-fold increase to about a 100-fold increase, about1.6-fold increase to about a 90-fold increase, about 1.6-fold increaseto about a 80-fold increase, about a 1.6-fold increase to about a70-fold increase, about a 1.6-fold increase to about a 60-fold increase,about a 1.6-fold increase to about a 50-fold increase, about a 1.6-foldincrease to about a 40-fold increase, about a 1.6-fold increase to abouta 30-fold increase, about 1.6-fold increase to about 20-fold increase,about a 1.6-fold increase to about a 9.5-fold increase, about a 1.6-foldincrease to about a 9.0-fold increase, about a 1.6-fold increase toabout a 8.5-fold increase, about a 1.6-fold increase to about a 8.0-foldincrease, about a 1.6-fold increase to about a 7.5-fold increase, abouta 1.6-fold increase to about a 7.0-fold increase, about a 1.6-foldincrease to about a 6.5-fold increase, about a 1.6-fold increase toabout a 6.0-fold increase, about a 1.6-fold increase to about a 5.5-foldincrease, about a 1.6-fold increase to about a 5.0-fold increase, abouta 1.6-fold increase to about a 4.5-fold increase, about a 1.6-foldincrease to about a 4.0-fold increase, about a 1.6-fold increase toabout a 3.5-fold increase, about 1.6-fold increase to about a 3.0-foldincrease, about a 1.6-fold increase to about a 2.8-fold increase, abouta 1.6-fold increase to about a 2.6-fold increase, about a 1.6-foldincrease to about a 2.5-fold increase, about a 1.6-fold increase toabout a 2.4-fold increase, about a 1.6-fold increase to about a 2.2-foldincrease, about a 1.6-fold increase to about a 2.0-fold increase, abouta 1.6-fold increase to about a 1.8-fold increase, about a 1.8-foldincrease to about a 100-fold increase, about 1.8-fold increase to abouta 90-fold increase, about 1.8-fold increase to about a 80-fold increase,about a 1.8-fold increase to about a 70-fold increase, about a 1.8-foldincrease to about a 60-fold increase, about a 1.8-fold increase to abouta 50-fold increase, about a 1.8-fold increase to about a 40-foldincrease, about a 1.8-fold increase to about a 30-fold increase, about1.8-fold increase to about 20-fold increase, about a 1.8-fold increaseto about a 10-fold increase, about a 1.8-fold increase to about a9.5-fold increase, about a 1.8-fold increase to about a 9.0-foldincrease, about a 1.8-fold increase to about a 8.5-fold increase, abouta 1.8-fold increase to about a 8.0-fold increase, about a 1.8-foldincrease to about a 7.5-fold increase, about a 1.8-fold increase toabout a 7.0-fold increase, about a 1.8-fold increase to about a 6.5-foldincrease, about a 1.8-fold increase to about a 6.0-fold increase, abouta 1.8-fold increase to about a 5.5-fold increase, about a 1.8-foldincrease to about a 5.0-fold increase, about a 1.8-fold increase toabout a 4.5-fold increase, about a 1.8-fold increase to about a 4.0-foldincrease, about a 1.8-fold increase to about a 3.5-fold increase, about1.8-fold increase to about a 3.0-fold increase, about a 1.8-foldincrease to about a 2.8-fold increase, about a 1.8-fold increase toabout a 2.6-fold increase, about a 1.8-fold increase to about a 2.5-foldincrease, about a 1.8-fold increase to about a 2.4-fold increase, abouta 1.8-fold increase to about a 2.2-fold increase, about a 1.8-foldincrease to about a 2.0-fold increase, about a 2.0-fold increase toabout a 100-fold increase, about 2.0-fold increase to about a 90-foldincrease, about 2.0-fold increase to about a 80-fold increase, about a2.0-fold increase to about a 70-fold increase, about a 2.0-fold increaseto about a 60-fold increase, about a 2.0-fold increase to about a50-fold increase, about a 2.0-fold increase to about a 40-fold increase,about a 2.0-fold increase to about a 30-fold increase, about 2.0-foldincrease to about 20-fold increase, about a 2.0-fold increase to about a10-fold increase, about a 2.0-fold increase to about a 9.5-foldincrease, about a 2.0-fold increase to about a 9.0-fold increase, abouta 2.0-fold increase to about a 8.5-fold increase, about a 2.0-foldincrease to about a 8.0-fold increase, about a 2.0-fold increase toabout a 7.5-fold increase, about a 2.0-fold increase to about a 7.0-foldincrease, about a 2.0-fold increase to about a 6.5-fold increase, abouta 2.0-fold increase to about a 6.0-fold increase, about a 2.0-foldincrease to about a 5.5-fold increase, about a 2.0-fold increase toabout a 5.0-fold increase, about a 2.0-fold increase to about a 4.5-foldincrease, about a 2.0-fold increase to about a 4.0-fold increase, abouta 2.0-fold increase to about a 3.5-fold increase, about 2.0-foldincrease to about a 3.0-fold increase, about a 2.0-fold increase toabout a 2.8-fold increase, about a 2.0-fold increase to about a 2.6-foldincrease, about a 2.0-fold increase to about a 2.5-fold increase, abouta 2.0-fold increase to about a 2.4-fold increase, about a 2.0-foldincrease to about a 2.2-fold increase, about a 2.2-fold increase toabout a 100-fold increase, about 2.2-fold increase to about a 90-foldincrease, about 2.2-fold increase to about a 80-fold increase, about a2.2-fold increase to about a 70-fold increase, about a 2.2-fold increaseto about a 60-fold increase, about a 2.2-fold increase to about a50-fold increase, about a 2.2-fold increase to about a 40-fold increase,about a 2.2-fold increase to about a 30-fold increase, about 2.2-foldincrease to about 20-fold increase, about a 2.2-fold increase to about a10-fold increase, about a 2.2-fold increase to about a 9.5-foldincrease, about a 2.2-fold increase to about a 9.0-fold increase, abouta 2.2-fold increase to about a 8.5-fold increase, about a 2.2-foldincrease to about a 8.0-fold increase, about a 2.2-fold increase toabout a 7.5-fold increase, about a 2.2-fold increase to about a 7.0-foldincrease, about a 2.2-fold increase to about a 6.5-fold increase, abouta 2.2-fold increase to about a 6.0-fold increase, about a 2.2-foldincrease to about a 5.5-fold increase, about a 2.2-fold increase toabout a 5.0-fold increase, about a 2.2-fold increase to about a 4.5-foldincrease, about a 2.2-fold increase to about a 4.0-fold increase, abouta 2.2-fold increase to about a 3.5-fold increase, about 2.2-foldincrease to about a 3.0-fold increase, about a 2.2-fold increase toabout a 2.8-fold increase, about a 2.2-fold increase to about a 2.6-foldincrease, about a 2.2-fold increase to about a 2.5-fold increase, abouta 2.2-fold increase to about a 2.4-fold increase, about a 2.4-foldincrease to about a 100-fold increase, about 2.4-fold increase to abouta 90-fold increase, about 2.4-fold increase to about a 80-fold increase,about a 2.4-fold increase to about a 70-fold increase, about a 2.4-foldincrease to about a 60-fold increase, about a 2.4-fold increase to abouta 50-fold increase, about a 2.4-fold increase to about a 40-foldincrease, about a 2.4-fold increase to about a 30-fold increase, about2.4-fold increase to about 20-fold increase, about a 2.4-fold increaseto about a 10-fold increase, about a 2.4-fold increase to about a9.5-fold increase, about a 2.4-fold increase to about a 9.0-foldincrease, about a 2.4-fold increase to about a 8.5-fold increase, abouta 2.4-fold increase to about a 8.0-fold increase, about a 2.4-foldincrease to about a 7.5-fold increase, about a 2.4-fold increase toabout a 7.0-fold increase, about a 2.4-fold increase to about a 6.5-foldincrease, about a 2.4-fold increase to about a 6.0-fold increase, abouta 2.4-fold increase to about a 5.5-fold increase, about a 2.4-foldincrease to about a 5.0-fold increase, about a 2.4-fold increase toabout a 4.5-fold increase, about a 2.4-fold increase to about a 4.0-foldincrease, about a 2.4-fold increase to about a 3.5-fold increase, about2.4-fold increase to about a 3.0-fold increase, about a 2.4-foldincrease to about a 2.8-fold increase, about a 2.4-fold increase toabout a 2.6-fold increase, about a 2.6-fold increase to about a 100-foldincrease, about 2.6-fold increase to about a 90-fold increase, about2.6-fold increase to about a 80-fold increase, about a 2.6-fold increaseto about a 70-fold increase, about a 2.6-fold increase to about a60-fold increase, about a 2.6-fold increase to about a 50-fold increase,about a 2.6-fold increase to about a 40-fold increase, about a 2.6-foldincrease to about a 30-fold increase, about 2.6-fold increase to about20-fold increase, about a 2.6-fold increase to about a 10-fold increase,about a 2.6-fold increase to about a 9.5-fold increase, about a 2.6-foldincrease to about a 9.0-fold increase, about a 2.6-fold increase toabout a 8.5-fold increase, about a 2.6-fold increase to about a 8.0-foldincrease, about a 2.6-fold increase to about a 7.5-fold increase, abouta 2.6-fold increase to about a 7.0-fold increase, about a 2.6-foldincrease to about a 6.5-fold increase, about a 2.6-fold increase toabout a 6.0-fold increase, about a 2.6-fold increase to about a 5.5-foldincrease, about a 2.6-fold increase to about a 5.0-fold increase, abouta 2.6-fold increase to about a 4.5-fold increase, about a 2.6-foldincrease to about a 4.0-fold increase, about a 2.6-fold increase toabout a 3.5-fold increase, about 2.6-fold increase to about a 3.0-foldincrease, about a 2.6-fold increase to about a 2.8-fold increase, abouta 2.8-fold increase to about a 100-fold increase, about 2.8-foldincrease to about a 90-fold increase, about 2.8-fold increase to about a80-fold increase, about a 2.8-fold increase to about a 70-fold increase,about a 2.8-fold increase to about a 60-fold increase, about a 2.8-foldincrease to about a 50-fold increase, about a 2.8-fold increase to abouta 40-fold increase, about a 2.8-fold increase to about a 30-foldincrease, about 2.8-fold increase to about 20-fold increase, about a2.8-fold increase to about a 10-fold increase, about a 2.8-fold increaseto about a 9.5-fold increase, about a 2.8-fold increase to about a9.0-fold increase, about a 2.8-fold increase to about a 8.5-foldincrease, about a 2.8-fold increase to about a 8.0-fold increase, abouta 2.8-fold increase to about a 7.5-fold increase, about a 2.8-foldincrease to about a 7.0-fold increase, about a 2.8-fold increase toabout a 6.5-fold increase, about a 2.8-fold increase to about a 6.0-foldincrease, about a 2.8-fold increase to about a 5.5-fold increase, abouta 2.8-fold increase to about a 5.0-fold increase, about a 2.8-foldincrease to about a 4.5-fold increase, about a 2.8-fold increase toabout a 4.0-fold increase, about a 2.8-fold increase to about a 3.5-foldincrease, about 2.8-fold increase to about a 3.0-fold increase, about a3.0-fold increase to about a 100-fold increase, about 3.0-fold increaseto about a 90-fold increase, about 3.0-fold increase to about a 80-foldincrease, about a 3.0-fold increase to about a 70-fold increase, about a3.0-fold increase to about a 60-fold increase, about a 3.0-fold increaseto about a 50-fold increase, about a 3.0-fold increase to about a40-fold increase, about a 3.0-fold increase to about a 30-fold increase,about 3.0-fold increase to about 20-fold increase, about a 3.0-foldincrease to about a 10-fold increase, about a 3.0-fold increase to abouta 9.5-fold increase, about a 3.0-fold increase to about a 9.0-foldincrease, about a 3.0-fold increase to about a 8.5-fold increase, abouta 3.0-fold increase to about a 8.0-fold increase, about a 3.0-foldincrease to about a 7.5-fold increase, about a 3.0-fold increase toabout a 7.0-fold increase, about a 3.0-fold increase to about a 6.5-foldincrease, about a 3.0-fold increase to about a 6.0-fold increase, abouta 3.0-fold increase to about a 5.5-fold increase, about a 3.0-foldincrease to about a 5.0-fold increase, about a 3.0-fold increase toabout a 4.5-fold increase, about a 3.0-fold increase to about a 4.0-foldincrease, about a 3.0-fold increase to about a 3.5-fold increase, abouta 3.5-fold increase to about a 100-fold increase, about 3.5-foldincrease to about a 90-fold increase, about 3.5-fold increase to about a80-fold increase, about a 3.5-fold increase to about a 70-fold increase,about a 3.5-fold increase to about a 60-fold increase, about a 3.5-foldincrease to about a 50-fold increase, about a 3.5-fold increase to abouta 40-fold increase, about a 3.5-fold increase to about a 30-foldincrease, about 3.5-fold increase to about 20-fold increase, about a3.5-fold increase to about a 10-fold increase, about a 3.5-fold increaseto about a 9.5-fold increase, about a 3.5-fold increase to about a9.0-fold increase, about a 3.5-fold increase to about a 8.5-foldincrease, about a 3.5-fold increase to about a 8.0-fold increase, abouta 3.5-fold increase to about a 7.5-fold increase, about a 3.5-foldincrease to about a 7.0-fold increase, about a 3.5-fold increase toabout a 6.5-fold increase, about a 3.5-fold increase to about a 6.0-foldincrease, about a 3.5-fold increase to about a 5.5-fold increase, abouta 3.5-fold increase to about a 5.0-fold increase, about a 3.5-foldincrease to about a 4.5-fold increase, about a 3.5-fold increase toabout a 4.0-fold increase, about a 4.0-fold increase to about a 100-foldincrease, about 4.0-fold increase to about a 90-fold increase, about4.0-fold increase to about a 80-fold increase, about a 4.0-fold increaseto about a 70-fold increase, about a 4.0-fold increase to about a60-fold increase, about a 4.0-fold increase to about a 50-fold increase,about a 4.0-fold increase to about a 40-fold increase, about a 4.0-foldincrease to about a 30-fold increase, about 4.0-fold increase to about20-fold increase, about a 4.0-fold increase to about a 10-fold increase,about a 4.0-fold increase to about a 9.5-fold increase, about a 4.0-foldincrease to about a 9.0-fold increase, about a 4.0-fold increase toabout a 8.5-fold increase, about a 4.0-fold increase to about a 8.0-foldincrease, about a 4.0-fold increase to about a 7.5-fold increase, abouta 4.0-fold increase to about a 7.0-fold increase, about a 4.0-foldincrease to about a 6.5-fold increase, about a 4.0-fold increase toabout a 6.0-fold increase, about a 4.0-fold increase to about a 5.5-foldincrease, about a 4.0-fold increase to about a 5.0-fold increase, abouta 4.0-fold increase to about a 4.5-fold increase, about a 4.5-foldincrease to about a 100-fold increase, about 4.5-fold increase to abouta 90-fold increase, about 4.5-fold increase to about a 80-fold increase,about a 4.5-fold increase to about a 70-fold increase, about a 4.5-foldincrease to about a 60-fold increase, about a 4.5-fold increase to abouta 50-fold increase, about a 4.5-fold increase to about a 40-foldincrease, about a 4.5-fold increase to about a 30-fold increase, about4.5-fold increase to about 20-fold increase, about a 4.5-fold increaseto about a 10-fold increase, about a 4.5-fold increase to about a9.5-fold increase, about a 4.5-fold increase to about a 9.0-foldincrease, about a 4.5-fold increase to about a 8.5-fold increase, abouta 4.5-fold increase to about a 8.0-fold increase, about a 4.5-foldincrease to about a 7.5-fold increase, about a 4.5-fold increase toabout a 7.0-fold increase, about a 4.5-fold increase to about a 6.5-foldincrease, about a 4.5-fold increase to about a 6.0-fold increase, abouta 4.5-fold increase to about a 5.5-fold increase, about a 4.5-foldincrease to about a 5.0-fold increase, about a 5.0-fold increase toabout a 100-fold increase, about 5.0-fold increase to about a 90-foldincrease, about 5.0-fold increase to about a 80-fold increase, about a5.0-fold increase to about a 70-fold increase, about a 5.0-fold increaseto about a 60-fold increase, about a 5.0-fold increase to about a50-fold increase, about a 5.0-fold increase to about a 40-fold increase,about a 5.0-fold increase to about a 30-fold increase, about 5.0-foldincrease to about 20-fold increase, about a 5.0-fold increase to about a10-fold increase, about a 5.0-fold increase to about a 9.5-foldincrease, about a 5.0-fold increase to about a 9.0-fold increase, abouta 5.0-fold increase to about a 8.5-fold increase, about a 5.0-foldincrease to about a 8.0-fold increase, about a 5.0-fold increase toabout a 7.5-fold increase, about a 5.0-fold increase to about a 7.0-foldincrease, about a 5.0-fold increase to about a 6.5-fold increase, abouta 5.0-fold increase to about a 6.0-fold increase, about a 5.0-foldincrease to about a 5.5-fold increase, about a 5.5-fold increase toabout a 100-fold increase, about 5.5-fold increase to about a 90-foldincrease, about 5.5-fold increase to about a 80-fold increase, about a5.5-fold increase to about a 70-fold increase, about a 5.5-fold increaseto about a 60-fold increase, about a 5.5-fold increase to about a50-fold increase, about a 5.5-fold increase to about a 40-fold increase,about a 5.5-fold increase to about a 30-fold increase, about 5.5-foldincrease to about 20-fold increase, about a 5.5-fold increase to about a10-fold increase, about a 5.5-fold increase to about a 9.5-foldincrease, about a 5.5-fold increase to about a 9.0-fold increase, abouta 5.5-fold increase to about a 8.5-fold increase, about a 5.5-foldincrease to about a 8.0-fold increase, about a 5.5-fold increase toabout a 7.5-fold increase, about a 5.5-fold increase to about a 7.0-foldincrease, about a 5.5-fold increase to about a 6.5-fold increase, abouta 5.5-fold increase to about a 6.0-fold increase, about a 6.0-foldincrease to about a 100-fold increase, about 6.0-fold increase to abouta 90-fold increase, about 6.0-fold increase to about a 80-fold increase,about a 6.0-fold increase to about a 70-fold increase, about a 6.0-foldincrease to about a 60-fold increase, about a 6.0-fold increase to abouta 50-fold increase, about a 6.0-fold increase to about a 40-foldincrease, about a 6.0-fold increase to about a 30-fold increase, about6.0-fold increase to about 20-fold increase, about a 6.0-fold increaseto about a 10-fold increase, about a 6.0-fold increase to about a9.5-fold increase, about a 6.0-fold increase to about a 9.0-foldincrease, about a 6.0-fold increase to about a 8.5-fold increase, abouta 6.0-fold increase to about a 8.0-fold increase, about a 6.0-foldincrease to about a 7.5-fold increase, about a 6.0-fold increase toabout a 7.0-fold increase, about a 6.0-fold increase to about a 6.5-foldincrease, about a 6.5-fold increase to about a 100-fold increase, about6.5-fold increase to about a 90-fold increase, about 6.5-fold increaseto about a 80-fold increase, about a 6.5-fold increase to about a70-fold increase, about a 6.5-fold increase to about a 60-fold increase,about a 6.5-fold increase to about a 50-fold increase, about a 6.5-foldincrease to about a 40-fold increase, about a 6.5-fold increase to abouta 30-fold increase, about 6.5-fold increase to about 20-fold increase,about a 6.5-fold increase to about a 10-fold increase, about a 6.5-foldincrease to about a 9.5-fold increase, about a 6.5-fold increase toabout a 9.0-fold increase, about a 6.5-fold increase to about a 8.5-foldincrease, about a 6.5-fold increase to about a 8.0-fold increase, abouta 6.5-fold increase to about a 7.5-fold increase, about a 6.5-foldincrease to about a 7.0-fold increase, about a 7.0-fold increase toabout a 100-fold increase, about 7.0-fold increase to about a 90-foldincrease, about 7.0-fold increase to about a 80-fold increase, about a7.0-fold increase to about a 70-fold increase, about a 7.0-fold increaseto about a 60-fold increase, about a 7.0-fold increase to about a50-fold increase, about a 7.0-fold increase to about a 40-fold increase,about a 7.0-fold increase to about a 30-fold increase, about 7.0-foldincrease to about 20-fold increase, about a 7.0-fold increase to about a10-fold increase, about a 7.0-fold increase to about a 9.5-foldincrease, about a 7.0-fold increase to about a 9.0-fold increase, abouta 7.0-fold increase to about a 8.5-fold increase, about a 7.0-foldincrease to about a 8.0-fold increase, about a 7.0-fold increase toabout a 7.5-fold increase, about a 7.5-fold increase to about a 100-foldincrease, about 7.5-fold increase to about a 90-fold increase, about7.5-fold increase to about a 80-fold increase, about a 7.5-fold increaseto about a 70-fold increase, about a 7.5-fold increase to about a60-fold increase, about a 7.5-fold increase to about a 50-fold increase,about a 7.5-fold increase to about a 40-fold increase, about a 7.5-foldincrease to about a 30-fold increase, about 7.5-fold increase to about20-fold increase, about a 7.5-fold increase to about a 10-fold increase,about a 7.5-fold increase to about a 9.5-fold increase, about a 7.5-foldincrease to about a 9.0-fold increase, about a 7.5-fold increase toabout a 8.5-fold increase, about a 7.5-fold increase to about a 8.0-foldincrease, about a 8.0-fold increase to about a 100-fold increase, about8.0-fold increase to about a 90-fold increase, about 8.0-fold increaseto about a 80-fold increase, about a 8.0-fold increase to about a70-fold increase, about a 8.0-fold increase to about a 60-fold increase,about a 8.0-fold increase to about a 50-fold increase, about a 8.0-foldincrease to about a 40-fold increase, about a 8.0-fold increase to abouta 30-fold increase, about 8.0-fold increase to about 20-fold increase,about a 8.0-fold increase to about a 10-fold increase, about a 8.0-foldincrease to about a 9.5-fold increase, about a 8.0-fold increase toabout a 9.0-fold increase, about a 8.0-fold increase to about a 8.5-foldincrease, about a 8.5-fold increase to about a 100-fold increase, about8.5-fold increase to about a 90-fold increase, about 8.5-fold increaseto about a 80-fold increase, about a 8.5-fold increase to about a70-fold increase, about a 8.5-fold increase to about a 60-fold increase,about a 8.5-fold increase to about a 50-fold increase, about a 8.5-foldincrease to about a 40-fold increase, about a 8.5-fold increase to abouta 30-fold increase, about 8.5-fold increase to about 20-fold increase,about a 8.5-fold increase to about a 10-fold increase, about a 8.5-foldincrease to about a 9.5-fold increase, about a 8.5-fold increase toabout a 9.0-fold increase, about a 9.0-fold increase to about a 100-foldincrease, about 9.0-fold increase to about a 90-fold increase, about9.0-fold increase to about a 80-fold increase, about a 9.0-fold increaseto about a 70-fold increase, about a 9.0-fold increase to about a60-fold increase, about a 9.0-fold increase to about a 50-fold increase,about a 9.0-fold increase to about a 40-fold increase, about a 9.0-foldincrease to about a 30-fold increase, about 9.0-fold increase to about20-fold increase, about a 9.0-fold increase to about a 10-fold increase,about a 9.0-fold increase to about a 9.5-fold increase, about a 9.5-foldincrease to about a 100-fold increase, about 9.5-fold increase to abouta 90-fold increase, about 9.5-fold increase to about a 80-fold increase,about a 9.5-fold increase to about a 70-fold increase, about a 9.5-foldincrease to about a 60-fold increase, about a 9.5-fold increase to abouta 50-fold increase, about a 9.5-fold increase to about a 40-foldincrease, about a 9.5-fold increase to about a 30-fold increase, about9.5-fold increase to about 20-fold increase, about a 9.5-fold increaseto about a 10-fold increase, about a 10-fold increase to about a100-fold increase, about 10-fold increase to about a 90-fold increase,about 10-fold increase to about a 80-fold increase, about a 10-foldincrease to about a 70-fold increase, about a 10-fold increase to abouta 60-fold increase, about a 10-fold increase to about a 50-foldincrease, about a 10-fold increase to about a 40-fold increase, about a10-fold increase to about a 30-fold increase, about 10-fold increase toabout 20-fold increase, about a 20-fold increase to about a 100-foldincrease, about 20-fold increase to about a 90-fold increase, about20-fold increase to about a 80-fold increase, about a 20-fold increaseto about a 70-fold increase, about a 20-fold increase to about a 60-foldincrease, about a 20-fold increase to about a 50-fold increase, about a20-fold increase to about a 40-fold increase, about a 20-fold increaseto about a 30-fold increase, about a 30-fold increase to about a100-fold increase, about 30-fold increase to about a 90-fold increase,about 30-fold increase to about a 80-fold increase, about a 30-foldincrease to about a 70-fold increase, about a 30-fold increase to abouta 60-fold increase, about a 30-fold increase to about a 50-foldincrease, about a 30-fold increase to about a 40-fold increase, about a40-fold increase to about a 100-fold increase, about 40-fold increase toabout a 90-fold increase, about 40-fold increase to about a 80-foldincrease, about a 40-fold increase to about a 70-fold increase, about a40-fold increase to about a 60-fold increase, about a 40-fold increaseto about a 50-fold increase, about a 50-fold increase to about a100-fold increase, about 50-fold increase to about a 90-fold increase,about 50-fold increase to about a 80-fold increase, about a 50-foldincrease to about a 70-fold increase, about a 50-fold increase to abouta 60-fold increase, about a 60-fold increase to about a 100-foldincrease, about 60-fold increase to about a 90-fold increase, about60-fold increase to about a 80-fold increase, about a 60-fold increaseto about a 70-fold increase, about a 70-fold increase to about a100-fold increase, about 70-fold increase to about a 90-fold increase,about 70-fold increase to about a 80-fold increase, about a 80-foldincrease to about a 100-fold increase, about 80-fold increase to about a90-fold increase, or about a 90-fold increase to about a 100-foldincrease) in toxin liberation in the target mammalian cell (e.g., any ofthe target mammalian cells described herein) as compared to acomposition including the same amount of a control ABPC (e.g., any ofthe exemplary control ABPCs described herein).

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 1%increase, at least a 2% increase, at least a 5% increase, at least a 10%increase, at least a 15% increase, at least a 20% increase, at least a25% increase, at least a 30% increase, at least a 35% increase, at leasta 40% increase, at least a 45% increase, at least a 50% increase, atleast a 55% increase, at least a 60% increase, at least a 65% increase,at least a 70% increase, at least a 75% increase, at least a 80%increase, at least a 85% increase, at least a 90% increase, at least a95% increase, at least a 100% increase, at least a 120% increase, atleast a 140% increase, at least a 160% increase, at least a 180%increase, at least a 200% increase, at least a 250% increase, at least a300% increase, at least a 350% increase, at least a 400% increase, atleast a 450% increase, at least a 500% increase, at least a 1,000%increase, at least a 2,000% increase, at least a 3,000% increase, atleast a 4,000% increase, at least a 5,000% increase, at least a 6,000%increase, at least a 7,000% increase, at least a 8,000% increase, at aleast a 9,000% increase, or at least a 10,000% increase, or about a 1%increase to about a 10,000% increase (e.g., or any of the subranges ofthis range described herein)) in target mammalian cell killing (e.g.,any of the exemplary target mammalian cells described herein) ascompared to a composition including the same amount of a control ABPC(e.g., any of the exemplary control ABPCs described herein).

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 0.1-foldincrease, at least a 0.2-fold increase, at least a 0.3-fold increase, atleast a 0.4-fold increase, at least a 0.5-fold increase, at least a0.6-fold increase, at least a 0.7-fold increase, at least a 0.8-foldincrease, at least a 0.9-fold increase, at least a 1.0-fold increase, atleast a 1.2-fold increase, at least a 1.4-fold increase, at least a1.5-fold increase, at least a 1.6-fold increase, at least a 1.8-foldincrease, at least a 2.0-fold increase, at least a 2.2-fold increase, atleast a 2.4-fold increase, at least a 2.5-fold increase, at least a2.6-fold increase, at least a 2.8-fold increase, at least a 3.0-foldincrease, at least a 3.5-fold increase, at least a 4.0-fold increase, atleast a 4.5-fold increase, at least a 5.0-fold increase, at least a5.5-fold increase, at least a 6.0-fold increase, at least a 6.5-foldincrease, at least a 7.0-fold increase, at least a 7.5-fold increase, atleast a 8.0-fold increase, at least a 8.5-fold increase, at least a9.0-fold increase, at least a 9.5-fold increase, at least a 10-foldincrease, at least a 15-fold increase, at least a 20-fold increase, atleast a 25-fold increase, at least a 30-fold increase, at least a35-fold increase, at least a 40-fold increase, at least a 40-foldincrease, at least a 45-fold increase, at least a 50-fold increase, atleast a 55-fold increase, at least a 60-fold increase, at least a65-fold increase, at least a 70-fold increase, at least a 80-foldincrease, at least a 85-fold increase, at least a 90-fold increase, atleast a 95-fold increase, or at least a 100-fold increase, or about a0.1-fold increase to about a 100-fold increase (or any of the subrangesof this range described herein)) in target mammalian cell killing (e.g.,any of the exemplary target mammalian cells described herein) ascompared to a composition including the same amount of a control ABPC(e.g., any of the exemplary control ABPCs described herein).

In some examples of any of the ABPCs described herein, a compositionincluding any of the ABPCs described herein (e.g., upon contactingtarget mammalian cells presenting FOLR1 on their surface) results indecreased (e.g., at least a 1% decrease, at least a 5% decrease, atleast a 10% decrease, at least a 15% decrease, at least a 20% decrease,at least a 25% decrease, at least a 30% decrease, at least a 35%decrease, at least a 40% decrease, at least a 45% decrease, at least a50% decrease, at least a 55% decrease, at least a 60% decrease, at leasta 65% decrease, at least a 70% decrease, at least a 75% decrease, atleast a 80% decrease, at least a 85% decrease, at least a 90% decrease,at least a 95% decrease, or at least a 99% decrease, about a 1% decreaseto about a 99% decrease, or any of the subranges of this range describedherein) IC50 (for target mammalian cell killing) as compared to the IC50for a composition including the same amount of a control ABPC (e.g., anyof the control ABPCs described herein) (e.g., upon contacting the sametarget mammalian cells).

In some examples of any of the ABPCs described herein, a compositionincluding any of the ABPCs described herein (e.g., upon contactingtarget mammalian cells presenting FOLR1 on their surface) can providefor an increase (e.g., at least a 0.1-fold increase, at least a 0.2-foldincrease, at least a 0.4-fold increase, at least a 0.6-fold increase, atleast a 0.8-fold increase, at least a 1-fold increase, at least a 2-foldincrease, at least a 5-fold increase, at least a 10-fold increase, atleast a 15-fold increase, at least a 20-fold increase, at least a25-fold increase, at least a 30-fold increase, at least a 35-foldincrease, at least a 40-fold increase, at least a 45-fold increase, atleast a 50-fold increase, at least a 55-fold increase, at least a60-fold increase, at least a 65-fold increase, at least a 70-foldincrease, at least a 75-fold increase, at least a 80-fold increase, atleast a 85-fold increase, at least a 90-fold increase, at least a95-fold increase, or at least a 100-fold increase, or about a 0.1-foldincrease to about 500-fold increase (or any of the subranges of thisrange described herein) in the ratio of K_(D) on target mammalian cellspresenting FOLR1 on their surface at a neutral pH (a pH of about 7.0 toabout 8.0) to IC50 at the neutral pH on the same target cells, e.g., ascompared to a control ABPC (e.g., any of the exemplary control ABPCsdescribed herein).

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 1%increase, at least a 2% increase, at least a 5% increase, at least a 10%increase, at least a 15% increase, at least a 20% increase, at least a25% increase, at least a 30% increase, at least a 35% increase, at leasta 40% increase, at least a 45% increase, at least a 50% increase, atleast a 55% increase, at least a 60% increase, at least a 65% increase,at least a 70% increase, at least a 75% increase, at least a 80%increase, at least a 85% increase, at least a 90% increase, at least a95% increase, at least a 100% increase, at least a 120% increase, atleast a 140% increase, at least a 160% increase, at least a 180%increase, at least a 200% increase, at least a 250% increase, at least a300% increase, at least a 350% increase, at least a 400% increase, atleast a 450% increase, at least a 500% increase, at least a 1,000%increase, at least a 2,000% increase, at least a 3,000% increase, atleast a 4,000% increase, at least a 5,000% increase, at least a 6,000%increase, at least a 7,000% increase, at least a 8,000% increase, atleast a 9,000% increase, or at least a 10,000% increase, or about a 1%increase to about a 10,000% increase (e.g., or any of the subranges ofthis range described herein)) in endolysosomal delivery in the targetmammalian cell (e.g., any of the exemplary target mammalian cellsdescribed herein) as compared to a composition including the same amountof a control ABPC (e.g., any of the exemplary control ABPCs describedherein).

In some examples of any of the ABPCs described herein, a compositionincluding the ABPC (e.g., any of the ABPCs described herein) can providefor an increase (e.g., a detectable increase) (e.g., at least a 0.1-foldincrease, at least a 0.2-fold increase, at least a 0.3-fold increase, atleast a 0.4-fold increase, at least a 0.5-fold increase, at least a0.6-fold increase, at least a 0.7-fold increase, at least a 0.8-foldincrease, at least a 0.9-fold increase, at least a 1.0-fold increase, atleast a 1.2-fold increase, at least a 1.4-fold increase, at least a1.5-fold increase, at least a 1.6-fold increase, at least a 1.8-foldincrease, at least a 2.0-fold increase, at least a 2.2-fold increase, atleast a 2.4-fold increase, at least a 2.5-fold increase, at least a2.6-fold increase, at least a 2.8-fold increase, at least a 3.0-foldincrease, at least a 3.5-fold increase, at least a 4.0-fold increase, atleast a 4.5-fold increase, at least a 5.0-fold increase, at least a5.5-fold increase, at least a 6.0-fold increase, at least a 6.5-foldincrease, at least a 7.0-fold increase, at least a 7.5-fold increase, atleast a 8.0-fold increase, at least a 8.5-fold increase, at least a9.0-fold increase, at least a 9.5-fold increase, at least a 10-foldincrease, at least a 15-fold increase, at least a 20-fold increase, atleast a 25-fold increase, at least a 30-fold increase, at least a35-fold increase, at least a 40-fold increase, at least a 45-foldincrease, at least a 50-fold increase, at least a 55-fold increase, atleast a 60-fold increase, at least a 65-fold increase, at least a70-fold increase, at least a 75-fold increase, at least a 80-foldincrease, at least a 85-fold increase, at least a 90-fold increase, atleast a 95-fold increase, or at least a 100-fold increase, or about a0.1-fold increase to about a 100-fold increase (or any of the subrangesof this range described herein)) in endolysosomal delivery in the targetmammalian cell (e.g., any of the exemplary target mammalian cellsdescribed herein) as compared to a composition including the same amountof a control ABPC (e.g., any of the exemplary control ABPCs describedherein).

In examples of any of the ABPCs described herein, the target mammaliancell does not express an FcRn receptor, or expresses a lower (e.g., adetectably lower) level (e.g., at least a 1% decreased, at least a 2%decreased, at least a 5% decreased, at least a 10% decrease, at least a15% decreased, at least a 20% decreased, at least a 25% decreased, atleast a 30% decreased, at least a 35% decreased, at least a 40%decreased, at least a 45% decreased, at least a 50% decreased, at leasta 55% decreased, at least a 60% decreased, at least a 65% decreased, atleast a 70% decreased, at least a 75% decreased, at least a 80%decreased, at least a 85% decreased, at least a 90% decreased, at leasta 95% decreased, or at least a 99% decreased level) of FcRn receptor ascompared to a FcRn expressing control cell (e.g., HUVEC— ThermoFisher#C0035C). In some examples of any of the ABPCs described herein, thetarget mammalian cell is a cancer cell. In some examples of any of theABPCs described herein, the ABPC is cytotoxic or cytostatic to thetarget mammalian cell.

In some examples of any of the ABPCs described herein, a compositionincluding any of the ABPCs described herein (e.g., upon administrationto a subject) results in less (e.g., a 1% decrease to about a 99%decrease, or any of the subranges of this range described herein) of areduction in the level of FOLR1 presented on the surface of the targetcell as compared to a composition including the same amount of a controlABPC (e.g., any of the control ABPCs described herein). In some examplesof any of the ABPCs described herein, the composition does not result ina detectable reduction in the level of the FOLR1 presented on thesurface of the target mammalian cell.

In some examples of any of the ABPCs described herein, the ABPC iscross-reactive with a non-human primate FOLR1 and a human FOLR1. In someexamples of any of the ABPCs described herein, the ABPC iscross-reactive with a non-human primate FOLR1, a human FOLR1, and one orboth of rat FOLR1 and a mouse FOLR1. In some examples of any of theABPCs described herein, the ABPC is cross-reactive with a non-humanprimate FOLR1, a human FOLR1, a rat FOLR1, and a mouse FOLR1. In someexamples of any of the ABPCs described herein, the ABPC iscross-reactive with mouse FOLR1 and rat FOLR1. In some examples of anyof the ABPCs described herein, the antigen-binding domain binds to anepitope of FOLR1 that is present on the surface of cells from an OldWorld Monkey.

Some examples of any of the ABPCs described herein can further include asecond antigen-binding domain (e.g., any of the exemplaryantigen-binding domains described herein). Non-limiting aspects of thesemethods are described below, and can be used in any combination withoutlimitation. Additional aspects of these methods are known in the art.

FOLR1 or Epitope of FOLR1

Folate Receptor 1 (FOLR1) is a tumor antigen that is known in the art,and is the target of therapeutic antibodies in oncology (Cheung A et al(2016) “Targeting folate receptor alpha for cancer treatment” Oncotarget7(32): 52553-52574). The sequence of the mature Human FOLR1 can be foundin SEQ ID NO: 9. The sequence of the cDNA encoding the mature HumanFOLR1 can be found in SEQ ID NO: 10. The sequence of the extracellulardomain of FOLR1 can be found in SEQ ID NO: 11. The sequence of the cDNAencoding the extracellular domain of FOLR1 can be found in SEQ ID NO:12.

Antigen-Binding Protein Constructs

Any of the antigen-binding protein constructs (ABPCs) described hereincan be a single polypeptide, or can include two, three, four, five, six,seven, eight, nine, or ten (the same or different) polypeptides. In someembodiments where the ABPC is a single polypeptide, the ABPC can includea single antigen-binding domain or two antigen-binding domains. In someembodiments where the ABPC is a single polypeptide and includes twoantigen-binding domains, the first and second antigen-binding domainscan be identical or different from each other (and can specifically bindto the same or different antigens or epitopes).

In some embodiments where the ABPC is a single polypeptide, the firstantigen-binding domain and the second antigen-binding domain (ifpresent) can each be independently selected from the group of: a VHdomain, a VHH domain, a VNAR domain, and a scFv. In some embodimentswhere the ABPC is a single polypeptide, the antigen-binding proteinconstruct can be a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART,a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody,scDiabody-HAS, a tandem-scFv, an Adnectin, a DARPin, a fibronectin, anda DEP conjugate. Additional examples of antigen-binding domains that canbe used when the ABPC is a single polypeptide are known in the art.

A V_(H)H domain is a single monomeric variable antibody domain that canbe found in camelids. A V_(NAR) domain is a single monomeric variableantibody domain that can be found in cartilaginous fish. Non-limitingaspects of V_(H)H domains and V_(NAR) domains are described in, e.g.,Cromie et al., Curr. Top. Med. Chem. 15:2543-2557, 2016; De Genst etal., Dev. Comp. Immunol. 30:187-198, 2006; De Meyer et al., TrendsBiotechnol. 32:263-270, 2014; Kijanka et al., Nanomedicine 10:161-174,2015; Kovaleva et al., Expert. Opin. Biol. Ther. 14:1527-1539, 2014;Krah et al., Immunopharmacol. Immunotoxicol. 38:21-28, 2016; Mujic-Delicet al., Trends Pharmacol. Sci. 35:247-255, 2014; Muyldermans, J.Biotechnol. 74:277-302, 2001; Muyldermans et al., Trends Biochem. Sci.26:230-235, 2001; Muyldermans, Ann. Rev. Biochem. 82:775-797, 2013;Rahbarizadeh et al., Immunol. Invest. 40:299-338, 2011; Van Audenhove etal., EBioMedicine 8:40-48, 2016; Van Bockstaele et al., Curr. Opin.Investig. Drugs 10:1212-1224, 2009; Vincke et al., Methods Mol. Biol.911:15-26, 2012; and Wesolowski et al., Med. Microbiol. Immunol.198:157-174, 2009.

In some embodiments where the ABPC is a single polypeptide and includestwo antigen-binding domains, the first antigen-binding domain and thesecond antigen-binding domain can both be VHH domains, or at least oneantigen-binding domain can be a VHH domain. In some embodiments wherethe ABPC is a single polypeptide and includes two antigen-bindingdomains, the first antigen-binding domain and the second antigen-bindingdomain are both V_(NAR) domains, or at least one antigen-binding domainis a V_(NAR) domain. In some embodiments where the ABPC is a singlepolypeptide, the first antigen-binding domain is a scFv domain. In someembodiments where the ABPC is a single polypeptide and includes twoantigen-binding domains, the first antigen-binding domain and the secondantigen-binding domain can both be scFv domains, or at least oneantigen-binding domain can be a scFv domain.

In some embodiments, the ABPC can include two or more polypeptides(e.g., two, three, four, five, six, seven, eight, nine, or tenpolypeptides). In some embodiments where the ABPC includes two or morepolypeptides, two, three, four, five or six of the polypeptides of thetwo or more polypeptides can be identical.

In some embodiments where the ABPC includes two or more polypeptides(e.g., two, three, four, five, six, seven, eight, nine, or tenpolypeptides), two or more of the polypeptides of the ABPC can assemble(e.g., non-covalently assemble) to form one or more antigen-bindingdomains, e.g., an antigen-binding fragment of an antibody (e.g., any ofthe antigen-binding fragments of an antibody described herein), aVHH-scAb, a VHH-Fab, a Dual scFab, a F(ab′)2, a diabody, a crossMab, aDAF (two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, aknobs-in-holes common light chain, a knobs-in-holes assembly, a chargepair, a Fab-arm exchange, a SEEDbody, a LUZ-Y, a Fcab, κλ-body, anorthogonal Fab, a DVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv,scFv-(L)IgG, IgG(L,H)-Fv, IgG(H)-V, V(H)—IgG, IgG(L)-V, V(L)-IgG, KIHIgG-scFab, 2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3,a triple body, a miniantibody, a minibody, a TriBi minibody, scFv-CH3KIH, Fab-scFv, a F(ab′)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalentHCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandemVHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, anImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, anAdnectin, a DARPin, a fibronectin, and a DEP conjugate. See, e.g.,Spiess et al., Mot Immunol. 67:95-106, 2015, incorporated in itsentirety herewith, for a description of these elements. Non-limitingexamples of an antigen-binding fragment of an antibody include an Fvfragment, a Fab fragment, a F(ab′)₂ fragment, and a Fab′ fragment.Additional examples of an antigen-binding fragment of an antibody is anantigen-binding fragment of an IgG (e.g., an antigen-binding fragment ofIgG1, IgG2, IgG3, or IgG4) (e.g., an antigen-binding fragment of a humanor humanized IgG, e.g., human or humanized IgG1, IgG2, IgG3, or IgG4);an antigen-binding fragment of an IgA (e.g., an antigen-binding fragmentof IgA1 or IgA2) (e.g., an antigen-binding fragment of a human orhumanized IgA, e.g., a human or humanized IgA1 or IgA2); anantigen-binding fragment of an IgD (e.g., an antigen-binding fragment ofa human or humanized IgD); an antigen-binding fragment of an IgE (e.g.,an antigen-binding fragment of a human or humanized IgE); or anantigen-binding fragment of an IgM (e.g., an antigen-binding fragment ofa human or humanized IgM).

A “Fv” fragment includes a non-covalently-linked dimer of one heavychain variable domain and one light chain variable domain.

A “Fab” fragment includes, the constant domain of the light chain andthe first constant domain (Cui) of the heavy chain, in addition to theheavy and light chain variable domains of the Fv fragment.

A “F(ab′)₂” fragment includes two Fab fragments joined, near the hingeregion, by disulfide bonds.

A “dual variable domain immunoglobulin” or “DVD-Ig” refers tomultivalent and multispecific binding proteins as described, e.g., inDiGiammarino et al., Methods Mol. Biol. 899:145-156, 2012; Jakob et al.,MABs 5:358-363, 2013; and U.S. Pat. Nos. 7,612,181; 8,258,268;8,586,714; 8,716,450; 8,722,855; 8,735,546; and 8,822,645, each of whichis incorporated by reference in its entirety.

DARTs are described in, e.g., Garber, Nature Reviews Drug Discovery13:799-801, 2014. Additional aspects of ABPCs are known in the art.

Antigen-Binding Domains

In some embodiments of any of the antigen-binding protein constructs(ABPCs) described herein, the dissociation rate of the firstantigen-binding domain (and optionally the second antigen-bindingdomain, if present) at a pH of about 4.0 to about 6.5 (e.g., about 4.0to about 6.4, about 4.0 to about 6.3, about 4.0 to about 6.2, about 4.0to about 6.1, about 4.0 to about 6.0, about 4.0 to about 5.9, about 4.0to about 5.8, about 4.0 to about 5.7, about 4.0 to about 5.6, about 4.0to about 5.5, about 4.0 to about 5.4, about 4.0 to about 5.3, about 4.0to about 5.2, about 4.0 to about 5.1, about 4.0 to about 5.0, about 4.0to about 4.9, about 4.0 to about 4.8, about 4.0 to about 4.7, about 4.0to about 4.6, about 4.0 to about 4.5, about 4.0 to about 4.4, about 4.0to about 4.3, about 4.0 to about 4.2, about 4.0 to about 4.1, about 4.1to about 6.5, about 4.1 to about 6.4, about 4.1 to about 6.3, about 4.1to about 6.2, about 4.1 to about 6.1, about 4.1 to about 6.0, about 4.1to about 5.9, about 4.1 to about 5.8, about 4.1 to about 5.7, about 4.1to about 5.6, about 4.1 to about 5.5, about 4.1 to about 5.4, about 4.1to about 5.3, about 4.1 to about 5.2, about 4.1 to about 5.1, about 4.1to about 5.0, about 4.1 to about 4.9, about 4.1 to about 4.8, about 4.1to about 4.7, about 4.1 to about 4.6, about 4.1 to about 4.5, about 4.1to about 4.4, about 4.1 to about 4.3, about 4.1 to about 4.2, about 4.2to about 6.5, about 4.2 to about 6.4, about 4.2 to about 6.3, about 4.2to about 6.2, about 4.2 to about 6.1, about 4.2 to about 6.0, about 4.2to about 5.9, about 4.2 to about 5.8, about 4.2 to about 5.7, about 4.2to about 5.6, about 4.2 to about 5.5, about 4.2 to about 5.4, about 4.2to about 5.3, about 4.2 to about 5.2, about 4.2 to about 5.1, about 4.2to about 5.0, about 4.2 to about 4.9, about 4.2 to about 4.8, about 4.2to about 4.7, about 4.2 to about 4.6, about 4.2 to about 4.5, about 4.2to about 4.4, about 4.2 to about 4.3, about 4.3 to about 6.5, about 4.3to about 6.4, about 4.3 to about 6.3, about 4.3 to about 6.2, about 4.3to about 6.1, about 4.3 to about 6.0, about 4.3 to about 5.9, about 4.3to about 5.8, about 4.3 to about 5.7, about 4.3 to about 5.6, about 4.3to about 5.5, about 4.3 to about 5.4, about 4.3 to about 5.3, about 4.3to about 5.2, about 4.3 to about 5.1, about 4.3 to about 5.0, about 4.3to about 4.9, about 4.3 to about 4.8, about 4.3 to about 4.7, about 4.3to about 4.6, about 4.3 to about 4.5, about 4.3 to about 4.4, about 4.4to about 6.5, about 4.4 to about 6.4, about 4.4 to about 6.3, about 4.4to about 6.2, about 4.4 to about 6.1, about 4.4 to about 6.0, about 4.4to about 5.9, about 4.4 to about 5.8, about 4.4 to about 5.7, about 4.4to about 5.6, about 4.4 to about 5.5, about 4.4 to about 5.4, about 4.4to about 5.3, about 4.4 to about 5.2, about 4.4 to about 5.1, about 4.4to about 5.0, about 4.4 to about 4.9, about 4.4 to about 4.8, about 4.4to about 4.7, about 4.4 to about 4.6, about 4.4 to about 4.5, about 4.5to about 6.5, about 4.5 to about 6.4, about 4.5 to about 6.3, about 4.5to about 6.2, about 4.5 to about 6.1, about 4.5 to about 6.0, about 4.5to about 5.9, about 4.5 to about 5.8, about 4.5 to about 5.7, about 4.5to about 5.6, about 4.5 to about 5.5, about 4.5 to about 5.4, about 4.5to about 5.3, about 4.5 to about 5.2, about 4.5 to about 5.1, about 4.5to about 5.0, about 4.5 to about 4.9, about 4.5 to about 4.8, about 4.5to about 4.7, about 4.5 to about 4.6, about 4.6 to about 6.5, about 4.6to about 6.4, about 4.6 to about 6.3, about 4.6 to about 6.2, about 4.6to about 6.1, about 4.6 to about 6.0, about 4.6 to about 5.9, about 4.6to about 5.8, about 4.6 to about 5.7, about 4.6 to about 5.6, about 4.6to about 5.5, about 4.6 to about 5.4, about 4.6 to about 5.3, about 4.6to about 5.2, about 4.6 to about 5.1, about 4.6 to about 5.0, about 4.6to about 4.9, about 4.6 to about 4.8, about 4.6 to about 4.7, about 4.7to about 6.5, about 4.7 to about 6.4, about 4.7 to about 6.3, about 4.7to about 6.2, about 4.7 to about 6.1, about 4.7 to about 6.0, about 4.7to about 5.9, about 4.7 to about 5.8, about 4.7 to about 5.7, about 4.7to about 5.6, about 4.7 to about 5.5, about 4.7 to about 5.4, about 4.7to about 5.3, about 4.7 to about 5.2, about 4.7 to about 5.1, about 4.7to about 5.0, about 4.7 to about 4.9, about 4.7 to about 4.8, about 4.8to about 6.5, about 4.8 to about 6.4, about 4.8 to about 6.3, about 4.8to about 6.2, about 4.8 to about 6.1, about 4.8 to about 6.0, about 4.8to about 5.9, about 4.8 to about 5.8, about 4.8 to about 5.7, about 4.8to about 5.6, about 4.8 to about 5.5, about 4.8 to about 5.4, about 4.8to about 5.3, about 4.8 to about 5.2, about 4.8 to about 5.1, about 4.8to about 5.0, about 4.8 to about 4.9, about 4.9 to about 6.5, about 4.9to about 6.4, about 4.9 to about 6.3, about 4.9 to about 6.2, about 4.9to about 6.1, about 4.9 to about 6.0, about 4.9 to about 5.9, about 4.9to about 5.8, about 4.9 to about 5.7, about 4.9 to about 5.6, about 4.9to about 5.5, about 4.9 to about 5.4, about 4.9 to about 5.3, about 4.9to about 5.2, about 4.9 to about 5.1, about 4.9 to about 5.0, about 5.0to about 6.5, about 5.0 to about 6.4, about 5.0 to about 6.3, about 5.0to about 6.2, about 5.0 to about 6.1, about 5.0 to about 6.0, about 5.0to about 5.9, about 5.0 to about 5.8, about 5.0 to about 5.7, about 5.0to about 5.6, about 5.0 to about 5.5, about 5.0 to about 5.4, about 5.0to about 5.3, about 5.0 to about 5.2, about 5.0 to about 5.1, about 5.1to about 6.5, about 5.1 to about 6.4, about 5.1 to about 6.3, about 5.1to about 6.2, about 5.1 to about 6.1, about 5.1 to about 6.0, about 5.1to about 5.9, about 5.1 to about 5.8, about 5.1 to about 5.7, about 5.1to about 5.6, about 5.1 to about 5.5, about 5.1 to about 5.4, about 5.1to about 5.3, about 5.1 to about 5.2, about 5.2 to about 6.5, about 5.2to about 6.4, about 5.2 to about 6.3, about 5.2 to about 6.2, about 5.2to about 6.1, about 5.2 to about 6.0, about 5.2 to about 5.9, about 5.2to about 5.8, about 5.2 to about 5.7, about 5.2 to about 5.6, about 5.2to about 5.5, about 5.2 to about 5.4, about 5.2 to about 5.3, about 5.3to about 6.5, about 5.3 to about 6.4, about 5.3 to about 6.3, about 5.3to about 6.2, about 5.3 to about 6.1, about 5.3 to about 6.0, about 5.3to about 5.9, about 5.3 to about 5.8, about 5.3 to about 5.7, about 5.3to about 5.6, about 5.3 to about 5.5, about 5.3 to about 5.4, about 5.4to about 6.5, about 5.4 to about 6.4, about 5.4 to about 6.3, about 5.4to about 6.2, about 5.4 to about 6.1, about 5.4 to about 6.0, about 5.4to about 5.9, about 5.4 to about 5.8, about 5.4 to about 5.7, about 5.4to about 5.6, about 5.4 to about 5.5, about 5.5 to about 6.5, about 5.5to about 6.4, about 5.5 to about 6.3, about 5.5 to about 6.2, about 5.5to about 6.1, about 5.5 to about 6.0, about 5.5 to about 5.9, about 5.5to about 5.8, about 5.5 to about 5.7, about 5.5 to about 5.6, about 5.6to about 6.5, about 5.6 to about 6.4, about 5.6 to about 6.3, about 5.6to about 6.2, about 5.6 to about 6.1, about 5.6 to about 6.0, about 5.6to about 5.9, about 5.6 to about 5.8, about 5.6 to about 5.7, about 5.7to about 6.5, about 5.7 to about 6.4, about 5.7 to about 6.3, about 5.7to about 6.2, about 5.7 to about 6.1, about 5.7 to about 6.0, about 5.7to about 5.9, about 5.7 to about 5.8, about 5.8 to about 6.5, about 5.8to about 6.4, about 5.8 to about 6.3, about 5.8 to about 6.2, about 5.8to about 6.1, about 5.8 to about 6.0, about 5.8 to about 5.9, about 5.9to about 6.5, about 5.9 to about 6.4, about 5.9 to about 6.3, about 5.9to about 6.2, about 5.9 to about 6.1, about 5.9 to about 6.0, about 6.0to about 6.5, about 6.0 to about 6.4, about 6.0 to about 6.3, about 6.0to about 6.2, about 6.0 to about 6.1, about 6.1 to about 6.5, about 6.1to about 6.4, about 6.1 to about 6.3, about 6.1 to about 6.2, about 6.2to about 6.5, about 6.2 to about 6.4, about 6.2 to about 6.3, about 6.3to about 6.5, about 6.3 to about 6.4, or about 6.4 to about 6.5) isfaster (e.g., (e.g., at least 5% faster, at least 10% faster, at least15% faster, at least 20%, at least 25% faster, at least 30% faster, atleast 35% faster, at least 40% faster, at least 45% faster, at least 50%faster, at least 55% faster, at least 60% faster, at least 65% faster;at least 70% faster, at least 75% faster, at least 80% faster, at least85% faster, at least 90% faster, at least 95% faster, at least 100%faster, at least 120% faster, at least 140% faster, at least 160%faster, at least 180% faster, at least 200% faster, at least 220% fasterat least 240% faster at least 260% faster at least 280% faster at least300% faster at least 320% faster at least 340% faster at least 360%faster at least 380% faster at least 400% faster at least 420% faster atleast 440% faster at least 460% faster at least 480% faster, at least500% faster, at least 1,000% faster, at least 2,000% faster, at least3,000% faster, at least 4,000% faster, at least 5,000%, at least 6,000%faster, at least 7,000% faster, at least 8,000% faster, at least 9,000%faster, or at least 10,000% faster, or about 5% faster to about 10,000%faster, about 5% faster to about 9,000% faster, about 5% faster to about8,000% faster, about 5% faster to about 7,000% faster, about 5% fasterto about 6,000% faster, about 5% faster to about 5,000% faster, about 5%faster to about 4,000% faster, about 5% faster to about 3,000% faster,about 5% faster to about 2,000% faster, about 5% faster to about 1,000%faster, about 5% faster to about 500% faster, about 5% faster to about480% faster, about 5% faster to about 460% faster, about 5% faster toabout 440% faster, about 5% faster to about 420% faster, about 5% fasterto about 400% faster, about 5% faster to about 380% faster, about 5%faster to about 360% faster, about 5% faster to about 340% faster, about5% faster to about 320% faster, about 5% faster to about 300% faster,about 5% faster to about 280% faster, about 5% faster to about 260%faster, about 5% faster to about 240% faster, about 5% faster to about220% faster, about 5% faster to about 200% faster, about 5% faster toabout 180% faster, about 5% faster to about 160% faster, about 5% fasterto about 140% faster, about 5% faster to about 120% faster, about 5%faster to about 100% faster, about 5% faster to about 95% faster, about5% faster to about 90% faster, about 5% faster to about 85% faster,about 5% faster to about 80% faster, about 5% faster to about 75%faster, about 5% faster to about 70% faster, about 5% faster to about65% faster, about 5% faster to about 60% faster, about 5% faster toabout 55% faster, about 5% faster to about 50% faster, about 5% fasterto about 45% faster, about 5% faster to about 40% faster, about 5%faster to about 35% faster, about 5% faster to about 30% faster, about5% faster to about 25% faster, about 5% faster to about 20% faster,about 5% faster to about 15% faster, about 5% faster to about 10%faster, about 10% faster to about 10,000% faster, about 10% faster toabout 9,000% faster, about 10% faster to about 8,000% faster, about 10%faster to about 7,000% faster, about 10% faster to about 6,000% faster,about 10% faster to about 5,000% faster, about 10% faster to about4,000% faster, about 10% faster to about 3,000% faster, about 10% fasterto about 2,000% faster, about 10% faster to about 1.000% faster, about10% faster to about 500% faster, about 10% faster to about 480% faster,about 10% faster to about 460% faster, about 10% faster to about 440%faster, about 10% faster to about 420% faster, about 10% faster to about400% faster, about 10% faster to about 380% faster, about 10% faster toabout 360% faster, about 10% faster to about 340% faster, about 10%faster to about 320% faster, about 10% faster to about 300% faster,about 10% faster to about 280% faster, about 10% faster to about 260%faster, about 10% faster to about 240% faster, about 10% faster to about220% faster, about 10% faster to about 200% faster, about 10% faster toabout 180% faster, about 10% faster to about 160% faster, about 10%faster to about 140% faster, about 10% faster to about 120% faster,about 10% faster to about 100% faster, about 10% faster to about 95%faster, about 10% faster to about 90% faster, about 10% faster to about85% faster, about 10% faster to about 80% faster, about 10% faster toabout 75% faster, about 10% faster to about 70% faster, about 10% fasterto about 65% faster, about 10% faster to about 60% faster, about 10%faster to about 55% faster, about 10% faster to about 50% faster, about10% faster to about 45% faster, about 10% faster to about 40% faster,about 10% faster to about 35% faster, about 10% faster to about 30%faster, about 10% faster to about 25% faster, about 10% faster to about20% faster, about 10% faster to about 15% faster, about 15% faster toabout 10,000% faster, about 15% faster to about 9,000% faster, about 15%faster to about 8,000% faster, about 15% faster to about 7,000% faster,about 15% faster to about 6,000% faster, about 15% faster to about5,000% faster, about 15% faster to about 4,000% faster, about 15% fasterto about 3,000% faster, about 15% faster to about 2,000% faster, about15% faster to about 1,000% faster, about 15% faster to about 500%faster, about 15% faster to about 480% faster, about 15% faster to about460% faster, about 15% faster to about 440% faster, about 15% faster toabout 420% faster, about 15% faster to about 400% faster, about 15%faster to about 380% faster, about 15% faster to about 360% faster,about 15% faster to about 340% faster, about 15% faster to about 320%faster, about 15% faster to about 300% faster, about 15% faster to about280% faster, about 15% faster to about 260% faster, about 15% faster toabout 240% faster, about 15% faster to about 220% faster, about 15%faster to about 200% faster, about 15% faster to about 180% faster,about 15% faster to about 160% faster, about 15% faster to about 140%faster, about 15% faster to about 120% faster, about 15% faster to about100% faster, about 15% faster to about 95% faster, about 15% faster toabout 90% faster, about 15% faster to about 85% faster, about 15% fasterto about 80% faster, about 15% faster to about 75% faster, about 15%faster to about 70% faster, about 15% faster to about 65% faster, about15% faster to about 60% faster, about 15% faster to about 55% faster,about 15% faster to about 50% faster, about 15% faster to about 45%faster, about 15% faster to about 40% faster, about 15% faster to about35% faster, about 15% faster to about 30% faster, about 15% faster toabout 25% faster, about 15% faster to about 20% faster, about 20% fasterto about 10,000% faster, about 20% faster to about 9,000% faster, about20% faster to about 8,000% faster, about 20% faster to about 7,000%faster, about 20% faster to about 6,000% faster, about 20% faster toabout 5,000% faster, about 20% faster to about 4,000% faster, about 20%faster to about 3,000% faster, about 20% faster to about 2,000% faster,about 20% faster to about 1,000% faster, about 20% faster to about 500%faster, about 20% faster to about 480% faster, about 20% faster to about460% faster, about 20% faster to about 440% faster, about 20% faster toabout 420% faster, about 20% faster to about 400% faster, about 20%faster to about 380% faster, about 20% faster to about 360% faster,about 20% faster to about 340% faster, about 20% faster to about 320%faster, about 20% faster to about 300% faster, about 20% faster to about280% faster, about 20% faster to about 260% faster, about 20% faster toabout 240% faster, about 20% faster to about 220% faster, about 20%faster to about 200% faster, about 20% faster to about 180% faster,about 20% faster to about 160% faster, about 20% faster to about 140%faster, about 20% faster to about 120% faster, about 20% faster to about100% faster, about 20% faster to about 95% faster, about 20% faster toabout 90% faster, about 20% faster to about 85% faster, about 20% fasterto about 80% faster, about 20% faster to about 75% faster, about 20%faster to about 70% faster, about 20% faster to about 65% faster, about20% faster to about 60% faster, about 20% faster to about 55% faster,about 20% faster to about 50% faster, about 20% faster to about 45%faster, about 20% faster to about 40% faster, about 20% faster to about35% faster, about 20% faster to about 30% faster, about 20% faster toabout 25% faster, about 25% faster to about 10,000% faster, about 25%faster to about 9,000% faster, about 25% faster to about 8,000% faster,about 25% faster to about 7,000% faster, about 25% faster to about6,000% faster, about 25% faster to about 5,000% faster, about 25% fasterto about 4,000% faster, about 25% faster to about 3,000% faster, about25% faster to about 2,000% faster, about 25% faster to about 1,000%faster, about 25% faster to about 500% faster, about 25% faster to about480% faster, about 25% faster to about 460% faster, about 25% faster toabout 440% faster, about 25% faster to about 420% faster, about 25%faster to about 400% faster, about 25% faster to about 380% faster,about 25% faster to about 360% faster, about 25% faster to about 340%faster, about 25% faster to about 320% faster, about 25% faster to about300% faster, about 25% faster to about 280% faster, about 25% faster toabout 260% faster, about 25% faster to about 240% faster, about 25%faster to about 220% faster, about 25% faster to about 200% faster,about 25% faster to about 180% faster, about 25% faster to about 160%faster, about 25% faster to about 140% faster, about 25% faster to about120% faster, about 25% faster to about 100% faster, about 25% faster toabout 95% faster, about 25% faster to about 90% faster, about 25% fasterto about 85% faster, about 25% faster to about 80% faster, about 25%faster to about 75% faster, about 25% faster to about 70% faster, about25% faster to about 65% faster, about 25% faster to about 60% faster,about 25% faster to about 55% faster, about 25% faster to about 50%faster, about 25% faster to about 45% faster, about 25% faster to about40% faster, about 25% faster to about 35% faster, about 25% faster toabout 30% faster, about 30% faster to about 10,000% faster, about 30%faster to about 9,000% faster, about 30% faster to about 8,000% faster,about 30% faster to about 7,000% faster, about 30% faster to about6.000% faster, about 30% faster to about 5,000% faster, about 30% fasterto about 4,000% faster, about 30% faster to about 3,000% faster, about30% faster to about 2,000% faster, about 30% faster to about 1,000%faster, about 30% faster to about 500% faster, about 30% faster to about480% faster, about 30% faster to about 460% faster, about 30% faster toabout 440% faster, about 30% faster to about 420% faster, about 30%faster to about 400% faster, about 30% faster to about 380% faster,about 30% faster to about 360% faster, about 30% faster to about 340%faster, about 30% faster to about 320% faster, about 30% faster to about300% faster, about 30% faster to about 280% faster, about 30% faster toabout 260% faster, about 30% faster to about 240% faster, about 30%faster to about 220% faster, about 30% faster to about 200% faster,about 30% faster to about 180% faster, about 30% faster to about 160%faster, about 30% faster to about 140% faster, about 30% faster to about120% faster, about 30% faster to about 100% faster, about 30% faster toabout 95% faster, about 30% faster to about 90% faster, about 30% fasterto about 85% faster, about 30% faster to about 80% faster, about 30%faster to about 75% faster, about 30% faster to about 70% faster, about30% faster to about 65% faster, about 30% faster to about 60% faster,about 30% faster to about 55% faster, about 30% faster to about 50%faster, about 30% faster to about 45% faster, about 30% faster to about40% faster, about 30% faster to about 35% faster, about 35% faster toabout 10,000% faster, about 35% faster to about 9,000% faster, about 35%faster to about 8,000% faster, about 35% faster to about 7,000% faster,about 35% faster to about 6,000% faster, about 35% faster to about5,000% faster, about 35% faster to about 4,000% faster, about 35% fasterto about 3,000% faster, about 35% faster to about 2,000% faster, about35% faster to about 1,000% faster, about 35% faster to about 500%faster, about 35% faster to about 480% faster, about 35% faster to about460% faster, about 35% faster to about 440% faster, about 35% faster toabout 420% faster, about 35% faster to about 400% faster, about 35%faster to about 380% faster, about 35% faster to about 360% faster,about 35% faster to about 340% faster, about 35% faster to about 320%faster, about 35% faster to about 300% faster, about 35% faster to about280% faster, about 35% faster to about 260% faster, about 35% faster toabout 240% faster, about 35% faster to about 220% faster, about 35%faster to about 200% faster, about 35% faster to about 180% faster,about 35% faster to about 160% faster, about 35% faster to about 140%faster, about 35% faster to about 120% faster, about 35% faster to about100% faster, about 35% faster to about 95% faster, about 35% faster toabout 90% faster, about 35% faster to about 85% faster, about 35% fasterto about 80% faster, about 35% faster to about 75% faster, about 35%faster to about 70% faster, about 35% faster to about 65% faster, about35% faster to about 60% faster, about 35% faster to about 55% faster,about 35% faster to about 50% faster, about 35% faster to about 45%faster, about 35% faster to about 40% faster, about 40% faster to about10,000% faster, about 40% faster to about 9,000% faster, about 40%faster to about 8,000% faster, about 40% faster to about 7,000% faster,about 40% faster to about 6,000% faster, about 40% faster to about5,000% faster, about 40% faster to about 4,000% faster, about 40% fasterto about 3,000% faster, about 40% faster to about 2,000% faster, about40% faster to about 1.000% faster, about 40% faster to about 500%faster, about 40% faster to about 480% faster, about 40% faster to about460% faster, about 40% faster to about 440% faster, about 40% faster toabout 420% faster, about 40% faster to about 400% faster, about 40%faster to about 380% faster, about 40% faster to about 360% faster,about 40% faster to about 340% faster, about 40% faster to about 320%faster, about 40% faster to about 300% faster, about 40% faster to about280% faster, about 40% faster to about 260% faster, about 40% faster toabout 240% faster, about 40% faster to about 220% faster, about 40%faster to about 200% faster, about 40% faster to about 180% faster,about 40% faster to about 160% faster, about 40% faster to about 140%faster, about 40% faster to about 120% faster, about 40% faster to about100% faster, about 40% faster to about 95% faster, about 40% faster toabout 90% faster, about 40% faster to about 85% faster, about 40% fasterto about 80% faster, about 40% faster to about 75% faster, about 40%faster to about 70% faster, about 40% faster to about 65% faster, about40% faster to about 60% faster, about 40% faster to about 55% faster,about 40% faster to about 50% faster, about 40% faster to about 45%faster, about 45% faster to about 10,000% faster, about 45% faster toabout 9,000% faster, about 45% faster to about 8,000% faster, about 45%faster to about 7,000% faster, about 45% faster to about 6,000% faster,about 45% faster to about 5,000% faster, about 45% faster to about4,000% faster, about 45% faster to about 3,000% faster, about 45% fasterto about 2,000% faster, about 45% faster to about 1,000% faster, about45% faster to about 500% faster, about 45% faster to about 480% faster,about 45% faster to about 460% faster, about 45% faster to about 440%faster, about 45% faster to about 420% faster, about 45% faster to about400% faster, about 45% faster to about 380% faster, about 45% faster toabout 360% faster, about 45% faster to about 340% faster, about 45%faster to about 320% faster, about 45% faster to about 300% faster,about 45% faster to about 280% faster, about 45% faster to about 260%faster, about 45% faster to about 240% faster, about 45% faster to about220% faster, about 45% faster to about 200% faster, about 45% faster toabout 180% faster, about 45% faster to about 160% faster, about 45%faster to about 140% faster, about 45% faster to about 120% faster,about 45% faster to about 100% faster, about 45% faster to about 95%faster, about 45% faster to about 90% faster, about 45% faster to about85% faster, about 45% faster to about 80% faster, about 45% faster toabout 75% faster, about 45% faster to about 70% faster, about 45% fasterto about 65% faster, about 45% faster to about 60% faster, about 45%faster to about 55% faster, about 45% faster to about 50% faster, about50% faster to about 10,000% faster, about 50% faster to about 9,000%faster, about 50% faster to about 8,000% faster, about 50% faster toabout 7,000% faster, about 50% faster to about 6,000% faster, about 50%faster to about 5,000% faster, about 50% faster to about 4,000% faster,about 50% faster to about 3,000% faster, about 50% faster to about2,000% faster, about 50% faster to about 1,000% faster, about 50% fasterto about 500% faster, about 50% faster to about 480% faster, about 50%faster to about 460% faster, about 50% faster to about 440% faster,about 50% faster to about 420% faster, about 50% faster to about 400%faster, about 50% faster to about 380% faster, about 50% faster to about360% faster, about 50% faster to about 340% faster, about 50% faster toabout 320% faster, about 50% faster to about 300% faster, about 50%faster to about 280% faster, about 50% faster to about 260% faster,about 50% faster to about 240% faster, about 50% faster to about 220%faster, about 50% faster to about 200% faster, about 50% faster to about180% faster, about 50% faster to about 160% faster, about 50% faster toabout 140% faster, about 50% faster to about 120% faster, about 50%faster to about 100% faster, about 50% faster to about 95% faster, about50% faster to about 90% faster, about 50% faster to about 85% faster,about 50% faster to about 80% faster, about 50% faster to about 75%faster, about 50% faster to about 70% faster, about 50% faster to about65% faster, about 50% faster to about 60% faster, about 50% faster toabout 55% faster, about 55% faster to about 10,000% faster, about 55%faster to about 9,000% faster, about 55% faster to about 8,000% faster,about 55% faster to about 7,000% faster, about 55% faster to about6,000% faster, about 55% faster to about 5,000% faster, about 55% fasterto about 4,000% faster, about 55% faster to about 3,000% faster, about55% faster to about 2,000% faster, about 55% faster to about 1,000%faster, about 55% faster to about 500% faster, about 55% faster to about480% faster, about 55% faster to about 460% faster, about 55% faster toabout 440% faster, about 55% faster to about 420% faster, about 55%faster to about 400% faster, about 55% faster to about 380% faster,about 55% faster to about 360% faster, about 55% faster to about 340%faster, about 55% faster to about 320% faster, about 55% faster to about300% faster, about 55% faster to about 280% faster, about 55% faster toabout 260% faster, about 55% faster to about 240% faster, about 55%faster to about 220% faster, about 55% faster to about 200% faster,about 55% faster to about 180% faster, about 55% faster to about 160%faster, about 55% faster to about 140% faster, about 55% faster to about120% faster, about 55% faster to about 100% faster, about 55% faster toabout 95% faster, about 55% faster to about 90% faster, about 55% fasterto about 85% faster, about 55% faster to about 80% faster, about 55%faster to about 75% faster, about 55% faster to about 70% faster, about55% faster to about 65% faster, about 55% faster to about 60% faster,about 60% faster to about 10,000% faster, about 60% faster to about9,000% faster, about 60% faster to about 8,000% faster, about 60% fasterto about 7,000% faster, about 60% faster to about 6,000% faster, about60% faster to about 5,000% faster, about 60% faster to about 4,000%faster, about 60% faster to about 3,000% faster, about 60% faster toabout 2,000% faster, about 60% faster to about 1,000% faster, about 60%faster to about 500% faster, about 60% faster to about 480% faster,about 60% faster to about 460% faster, about 60% faster to about 440%faster, about 60% faster to about 420% faster, about 60% faster to about400% faster, about 60% faster to about 380% faster, about 60% faster toabout 360% faster, about 60% faster to about 340% faster, about 60%faster to about 320% faster, about 60% faster to about 300% faster,about 60% faster to about 280% faster, about 60% faster to about 260%faster, about 60% faster to about 240% faster, about 60% faster to about220% faster, about 60% faster to about 200% faster, about 60% faster toabout 180% faster, about 60% faster to about 160% faster, about 60%faster to about 140% faster, about 60% faster to about 120% faster,about 60% faster to about 100% faster, about 60% faster to about 95%faster, about 60% faster to about 90% faster, about 60% faster to about85% faster, about 60% faster to about 80% faster, about 60% faster toabout 75% faster, about 60% faster to about 70% faster, about 60% fasterto about 65% faster, about 65% faster to about 10,000% faster, about 65%faster to about 9,000% faster, about 65% faster to about 8,000% faster,about 65% faster to about 7,000% faster, about 65% faster to about6,000% faster, about 65% faster to about 5,000% faster, about 65% fasterto about 4,000% faster, about 65% faster to about 3,000% faster, about65% faster to about 2,000% faster, about 65% faster to about 1.000%faster, about 65% faster to about 500% faster, about 65% faster to about480% faster, about 65% faster to about 460% faster, about 65% faster toabout 440% faster, about 65% faster to about 420% faster, about 65%faster to about 400% faster, about 65% faster to about 380% faster,about 65% faster to about 360% faster, about 65% faster to about 340%faster, about 65% faster to about 320% faster, about 65% faster to about300% faster, about 65% faster to about 280% faster, about 65% faster toabout 260% faster, about 65% faster to about 240% faster, about 65%faster to about 220% faster, about 65% faster to about 200% faster,about 65% faster to about 180% faster, about 65% faster to about 160%faster, about 65% faster to about 140% faster, about 65% faster to about120% faster, about 65% faster to about 100% faster, about 65% faster toabout 95% faster, about 65% faster to about 90% faster, about 65% fasterto about 85% faster, about 65% faster to about 80% faster, about 65%faster to about 75% faster, about 65% faster to about 70% faster, about70% faster to about 10,000% faster, about 70% faster to about 9,000%faster, about 70% faster to about 8,000% faster, about 70% faster toabout 7,000% faster, about 70% faster to about 6,000% faster, about 70%faster to about 5,000% faster, about 70% faster to about 4,000% faster,about 70% faster to about 3,000% faster, about 70% faster to about2,000% faster, about 70% faster to about 1,000% faster, about 70% fasterto about 500% faster, about 70% faster to about 480% faster, about 70%faster to about 460% faster, about 70% faster to about 440% faster,about 70% faster to about 420% faster, about 70% faster to about 400%faster, about 70% faster to about 380% faster, about 70% faster to about360% faster, about 70% faster to about 340% faster, about 70% faster toabout 320% faster, about 70% faster to about 300% faster, about 70%faster to about 280% faster, about 70% faster to about 260% faster,about 70% faster to about 240% faster, about 70% faster to about 220%faster, about 70% faster to about 200% faster, about 70% faster to about180% faster, about 70% faster to about 160% faster, about 70% faster toabout 140% faster, about 70% faster to about 120% faster, about 70%faster to about 100% faster, about 70% faster to about 95% faster, about70% faster to about 90% faster, about 70% faster to about 85% faster,about 70% faster to about 80% faster, about 70% faster to about 75%faster, about 75% faster to about 10,000% faster, about 75% faster toabout 9,000% faster, about 75% faster to about 8,000% faster, about 75%faster to about 7,000% faster, about 75% faster to about 6,000% faster,about 75% faster to about 5,000% faster, about 75% faster to about4,000% faster, about 75% faster to about 3,000% faster, about 75% fasterto about 2,000% faster, about 75% faster to about 1,000% faster, about75% faster to about 500% faster, about 75% faster to about 480% faster,about 75% faster to about 460% faster, about 75% faster to about 440%faster, about 75% faster to about 420% faster, about 75% faster to about400% faster, about 75% faster to about 380% faster, about 75% faster toabout 360% faster, about 75% faster to about 340% faster, about 75%faster to about 320% faster, about 75% faster to about 300% faster,about 75% faster to about 280% faster, about 75% faster to about 260%faster, about 75% faster to about 240% faster, about 75% faster to about220% faster, about 75% faster to about 200% faster, about 75% faster toabout 180% faster, about 75% faster to about 160% faster, about 75%faster to about 140% faster, about 75% faster to about 120% faster,about 75% faster to about 100% faster, about 75% faster to about 95%faster, about 75% faster to about 90% faster, about 75% faster to about85% faster, about 75% faster to about 80% faster, about 80% faster toabout 10,000% faster, about 80% faster to about 9,000% faster, about 80%faster to about 8,000% faster, about 80% faster to about 7,000% faster,about 80% faster to about 6,000% faster, about 80% faster to about5,000% faster, about 80% faster to about 4,000% faster, about 80% fasterto about 3,000% faster, about 80% faster to about 2,000% faster, about80% faster to about 1,000% faster, about 80% faster to about 500%faster, about 80% faster to about 480% faster, about 80% faster to about460% faster, about 80% faster to about 440% faster, about 80% faster toabout 420% faster, about 80% faster to about 400% faster, about 80%faster to about 380% faster, about 80% faster to about 360% faster,about 80% faster to about 340% faster, about 80% faster to about 320%faster, about 80% faster to about 300% faster, about 80% faster to about280% faster, about 80% faster to about 260% faster, about 80% faster toabout 240% faster, about 80% faster to about 220% faster, about 80%faster to about 200% faster, about 80% faster to about 180% faster,about 80% faster to about 160% faster, about 80% faster to about 140%faster, about 80% faster to about 120% faster, about 80% faster to about100% faster, about 80% faster to about 95% faster, about 80% faster toabout 90% faster, about 80% faster to about 85% faster, about 85% fasterto about 10,000% faster, about 85% faster to about 9,000% faster, about85% faster to about 8,000% faster, about 85% faster to about 7,000%faster, about 85% faster to about 6,000% faster, about 85% faster toabout 5,000% faster, about 85% faster to about 4,000% faster, about 85%faster to about 3,000% faster, about 85% faster to about 2,000% faster,about 85% faster to about 1.000% faster, about 85% faster to about 500%faster, about 85% faster to about 480% faster, about 85% faster to about460% faster, about 85% faster to about 440% faster, about 85% faster toabout 420% faster, about 85% faster to about 400% faster, about 85%faster to about 380% faster, about 85% faster to about 360% faster,about 85% faster to about 340% faster, about 85% faster to about 320%faster, about 85% faster to about 300% faster, about 85% faster to about280% faster, about 85% faster to about 260% faster, about 85% faster toabout 240% faster, about 85% faster to about 220% faster, about 85%faster to about 200% faster, about 85% faster to about 180% faster,about 85% faster to about 160% faster, about 85% faster to about 140%faster, about 85% faster to about 120% faster, about 85% faster to about100% faster, about 85% faster to about 95% faster, about 85% faster toabout 90% faster, about 90% faster to about 10,000% faster, about 90%faster to about 9,000% faster, about 90% faster to about 8,000% faster,about 90% faster to about 7,000% faster, about 90% faster to about6,000% faster, about 90% faster to about 5,000% faster, about 90% fasterto about 4,000% faster, about 90% faster to about 3,000% faster, about90% faster to about 2,000% faster, about 90% faster to about 1,000%faster, about 90% faster to about 500% faster, about 90% faster to about480% faster, about 90% faster to about 460% faster, about 90% faster toabout 440% faster, about 90% faster to about 420% faster, about 90%faster to about 400% faster, about 90% faster to about 380% faster,about 90% faster to about 360% faster, about 90% faster to about 340%faster, about 90% faster to about 320% faster, about 90% faster to about300% faster, about 90% faster to about 280% faster, about 90% faster toabout 260% faster, about 90% faster to about 240% faster, about 90%faster to about 220% faster, about 90% faster to about 200% faster,about 90% faster to about 180% faster, about 90% faster to about 160%faster, about 90% faster to about 140% faster, about 90% faster to about120% faster, about 90% faster to about 100% faster, about 90% faster toabout 95% faster, about 95% faster to about 10,000% faster, about 95%faster to about 9,000% faster, about 95% faster to about 8,000% faster,about 95% faster to about 7,000% faster, about 95% faster to about6,000% faster, about 95% faster to about 5,000% faster, about 95% fasterto about 4,000% faster, about 95% faster to about 3,000% faster, about95% faster to about 2,000% faster, about 95% faster to about 1,000%faster, about 95% faster to about 500% faster, about 95% faster to about480% faster, about 95% faster to about 460% faster, about 95% faster toabout 440% faster, about 95% faster to about 420% faster, about 95%faster to about 400% faster, about 95% faster to about 380% faster,about 95% faster to about 360% faster, about 95% faster to about 340%faster, about 95% faster to about 320% faster, about 95% faster to about300% faster, about 95% faster to about 280% faster, about 95% faster toabout 260% faster, about 95% faster to about 240% faster, about 95%faster to about 220% faster, about 95% faster to about 200% faster,about 95% faster to about 180% faster, about 95% faster to about 160%faster, about 95% faster to about 140% faster, about 95% faster to about120% faster, about 95% faster to about 100% faster, about 100% faster toabout 10,000% faster, about 100% faster to about 9,000% faster, about100% faster to about 8,000% faster, about 100% faster to about 7,000%faster, about 100% faster to about 6,000% faster, about 100% faster toabout 5,000% faster, about 100% faster to about 4,000% faster, about100% faster to about 3,000% faster, about 100% faster to about 2,000%faster, about 100% faster to about 1,000% faster, about 100% faster toabout 500% faster, about 100% faster to about 480% faster, about 100%faster to about 460% faster, about 100% faster to about 440% faster,about 100% faster to about 420% faster, about 100% faster to about 400%faster, about 100% faster to about 380% faster, about 100% faster toabout 360% faster, about 100% faster to about 340% faster, about 100%faster to about 320% faster, about 100% faster to about 300% faster,about 100% faster to about 280% faster, about 100% faster to about 260%faster, about 100% faster to about 240% faster, about 100% faster toabout 220% faster, about 100% faster to about 200% faster, about 100%faster to about 180% faster, about 100% faster to about 160% faster,about 100% faster to about 140% faster, about 100% faster to about 120%faster, about 120% faster to about 10,000% faster, about 120% faster toabout 9,000% faster, about 120% faster to about 8,000% faster, about120% faster to about 7,000% faster, about 120% faster to about 6,000%faster, about 120% faster to about 5,000% faster, about 120% faster toabout 4,000% faster, about 120% faster to about 3,000% faster, about120% faster to about 2,000% faster, about 120% faster to about 1,000%faster, about 120% faster to about 500% faster, about 120% faster toabout 480% faster, about 120% faster to about 460% faster, about 120%faster to about 440% faster, about 120% faster to about 420% faster,about 120% faster to about 400% faster, about 120% faster to about 380%faster, about 120% faster to about 360% faster, about 120% faster toabout 340% faster, about 120% faster to about 320% faster, about 120%faster to about 300% faster, about 120% faster to about 280% faster,about 120% faster to about 260% faster, about 120% faster to about 240%faster, about 120% faster to about 220% faster, about 120% faster toabout 200% faster, about 120% faster to about 180% faster, about 120%faster to about 160% faster, about 120% faster to about 140% faster,about 140% faster to about 10,000% faster, about 140% faster to about9,000% faster, about 140% faster to about 8,000% faster, about 140%faster to about 7,000% faster, about 140% faster to about 6,000% faster,about 140% faster to about 5,000% faster, about 140% faster to about4,000% faster, about 140% faster to about 3,000% faster, about 140%faster to about 2,000% faster, about 140% faster to about 1,000% faster,about 140% faster to about 500% faster, about 140% faster to about 480%faster, about 140% faster to about 460% faster, about 140% faster toabout 440% faster, about 140% faster to about 420% faster, about 140%faster to about 400% faster, about 140% faster to about 380% faster,about 140% faster to about 360% faster, about 140% faster to about 340%faster, about 140% faster to about 320% faster, about 140% faster toabout 300% faster, about 140% faster to about 280% faster, about 140%faster to about 260% faster, about 140% faster to about 240% faster,about 140% faster to about 220% faster, about 140% faster to about 200%faster, about 140% faster to about 180% faster, about 140% faster toabout 160% faster, about 160% faster to about 10,000% faster, about 160%faster to about 9,000% faster, about 160% faster to about 8,000% faster,about 160% faster to about 7,000% faster, about 160% faster to about6,000% faster, about 160% faster to about 5,000% faster, about 160%faster to about 4,000% faster, about 160% faster to about 3,000% faster,about 160% faster to about 2,000% faster, about 160% faster to about1,000% faster, about 160% faster to about 500% faster, about 160% fasterto about 480% faster, about 160% faster to about 460% faster, about 160%faster to about 440% faster, about 160% faster to about 420% faster,about 160% faster to about 400% faster, about 160% faster to about 380%faster, about 160% faster to about 360% faster, about 160% faster toabout 340% faster, about 160% faster to about 320% faster, about 160%faster to about 300% faster, about 160% faster to about 280% faster,about 160% faster to about 260% faster, about 160% faster to about 240%faster, about 160% faster to about 220% faster, about 160% faster toabout 200% faster, about 160% faster to about 180% faster, about 180%faster to about 10,000% faster, about 180% faster to about 9,000%faster, about 180% faster to about 8,000% faster, about 180% faster toabout 7,000% faster, about 180% faster to about 6,000% faster, about180% faster to about 5,000% faster, about 180% faster to about 4,000%faster, about 180% faster to about 3,000% faster, about 180% faster toabout 2,000% faster, about 180% faster to about 1,000% faster, about180% faster to about 500% faster, about 180% faster to about 480%faster, about 180% faster to about 460% faster, about 180% faster toabout 440% faster, about 180% faster to about 420% faster, about 180%faster to about 400% faster, about 180% faster to about 380% faster,about 180% faster to about 360% faster, about 180% faster to about 340%faster, about 180% faster to about 320% faster, about 180% faster toabout 300% faster, about 180% faster to about 280% faster, about 180%faster to about 260% faster, about 180% faster to about 240% faster,about 180% faster to about 220% faster, about 180% faster to about 200%faster, about 200% faster to about 10,000% faster, about 200% faster toabout 9,000% faster, about 200% faster to about 8,000% faster, about200% faster to about 7,000% faster, about 200% faster to about 6,000%faster, about 200% faster to about 5,000% faster, about 200% faster toabout 4,000% faster, about 200% faster to about 3,000% faster, about200% faster to about 2,000% faster, about 200% faster to about 1,000%faster, about 200% faster to about 500% faster, about 200% faster toabout 480% faster, about 200% faster to about 460% faster, about 200%faster to about 440% faster, about 200% faster to about 420% faster,about 200% faster to about 400% faster, about 200% faster to about 380%faster, about 200% faster to about 360% faster, about 200% faster toabout 340% faster, about 200% faster to about 320% faster, about 200%faster to about 300% faster, about 200% faster to about 280% faster,about 200% faster to about 260% faster, about 200% faster to about 240%faster, about 200% faster to about 220% faster, about 220% faster toabout 10,000% faster, about 220% faster to about 9,000% faster, about220% faster to about 8,000% faster, about 220% faster to about 7,000%faster, about 220% faster to about 6,000% faster, about 220% faster toabout 5,000% faster, about 220% faster to about 4,000% faster, about220% faster to about 3,000% faster, about 220% faster to about 2,000%faster, about 220% faster to about 1,000% faster, about 220% faster toabout 500% faster, about 220% faster to about 480% faster, about 220%faster to about 460% faster, about 220% faster to about 440% faster,about 220% faster to about 420% faster, about 220% faster to about 400%faster, about 220% faster to about 380% faster, about 220% faster toabout 360% faster, about 220% faster to about 340% faster, about 220%faster to about 320% faster, about 220% faster to about 300% faster,about 220% faster to about 280% faster, about 220% faster to about 260%faster, about 220% faster to about 240% faster, about 240% faster toabout 10,000% faster, about 240% faster to about 9,000% faster, about240% faster to about 8,000% faster, about 240% faster to about 7,000%faster, about 240% faster to about 6,000% faster, about 240% faster toabout 5,000% faster, about 240% faster to about 4,000% faster, about240% faster to about 3,000% faster, about 240% faster to about 2,000%faster, about 240% faster to about 1,000% faster, about 240% faster toabout 500% faster, about 240% faster to about 480% faster, about 240%faster to about 460% faster, about 240% faster to about 440% faster,about 240% faster to about 420% faster, about 240% faster to about 400%faster, about 240% faster to about 380% faster, about 240% faster toabout 360% faster, about 240% faster to about 340% faster, about 240%faster to about 320% faster, about 240% faster to about 300% faster,about 240% faster to about 280% faster, about 240% faster to about 260%faster, about 260% faster to about 10,000% faster, about 260% faster toabout 9,000% faster, about 260% faster to about 8,000% faster, about260% faster to about 7,000% faster, about 260% faster to about 6,000%faster, about 260% faster to about 5,000% faster, about 260% faster toabout 4,000% faster, about 260% faster to about 3,000% faster, about260% faster to about 2,000% faster, about 260% faster to about 1,000%faster, about 260% faster to about 500% faster, about 260% faster toabout 480% faster, about 260% faster to about 460% faster, about 260%faster to about 440% faster, about 260% faster to about 420% faster,about 260% faster to about 400% faster, about 260% faster to about 380%faster, about 260% faster to about 360% faster, about 260% faster toabout 340% faster, about 260% faster to about 320% faster, about 260%faster to about 300% faster, about 260% faster to about 280% faster,about 280% faster to about 10,000% faster, about 280% faster to about9,000% faster, about 280% faster to about 8,000% faster, about 280%faster to about 7,000% faster, about 280% faster to about 6,000% faster,about 280% faster to about 5,000% faster, about 280% faster to about4,000% faster, about 280% faster to about 3,000% faster, about 280%faster to about 2,000% faster, about 280% faster to about 1,000% faster,about 280% faster to about 500% faster, about 280% faster to about 480%faster, about 280% faster to about 460% faster, about 280% faster toabout 440% faster, about 280% faster to about 420% faster, about 280%faster to about 400% faster, about 280% faster to about 380% faster,about 280% faster to about 360% faster, about 280% faster to about 340%faster, about 280% faster to about 320% faster, about 280% faster toabout 300% faster, about 300% faster to about 10,000% faster, about 300%faster to about 9,000% faster, about 300% faster to about 8,000% faster,about 300% faster to about 7,000% faster, about 300% faster to about6,000% faster, about 300% faster to about 5,000% faster, about 300%faster to about 4,000% faster, about 300% faster to about 3,000% faster,about 300% faster to about 2,000% faster, about 300% faster to about1,000% faster, about 300% faster to about 500% faster, about 300% fasterto about 480% faster, about 300% faster to about 460% faster, about 300%faster to about 440% faster, about 300% faster to about 420% faster,about 300% faster to about 400% faster, about 300% faster to about 380%faster, about 300% faster to about 360% faster, about 300% faster toabout 340% faster, about 300% faster to about 320% faster, about 320%faster to about 10,000% faster, about 320% faster to about 9,000%faster, about 320% faster to about 8,000% faster, about 320% faster toabout 7,000% faster, about 320% faster to about 6,000% faster, about320% faster to about 5,000% faster, about 320% faster to about 4,000%faster, about 320% faster to about 3,000% faster, about 320% faster toabout 2,000% faster, about 320% faster to about 1,000% faster, about320% faster to about 500% faster, about 320% faster to about 480%faster, about 320% faster to about 460% faster, about 320% faster toabout 440% faster, about 320% faster to about 420% faster, about 320%faster to about 400% faster, about 320% faster to about 380% faster,about 320% faster to about 360% faster, about 320% faster to about 340%faster, about 340% faster to about 10,000% faster, about 340% faster toabout 9,000% faster, about 340% faster to about 8,000% faster, about340% faster to about 7,000% faster, about 340% faster to about 6,000%faster, about 340% faster to about 5,000% faster, about 340% faster toabout 4,000% faster, about 340% faster to about 3,000% faster, about340% faster to about 2,000% faster, about 340% faster to about 1,000%faster, about 340% faster to about 500% faster, about 340% faster toabout 480% faster, about 340% faster to about 460% faster, about 340%faster to about 440% faster, about 340% faster to about 420% faster,about 340% faster to about 400% faster, about 340% faster to about 380%faster, about 340% faster to about 360% faster, about 360% faster toabout 10,000% faster, about 360% faster to about 9,000% faster, about360% faster to about 8,000% faster, about 360% faster to about 7,000%faster, about 360% faster to about 6,000% faster, about 360% faster toabout 5,000% faster, about 360% faster to about 4,000% faster, about360% faster to about 3,000% faster, about 360% faster to about 2,000%faster, about 360% faster to about 1,000% faster, about 360% faster toabout 500% faster, about 360% faster to about 480% faster, about 360%faster to about 460% faster, about 360% faster to about 440% faster,about 360% faster to about 420% faster, about 360% faster to about 400%faster, about 360% faster to about 380% faster, about 380% faster toabout 10,000% faster, about 380% faster to about 9,000% faster, about380% faster to about 8,000% faster, about 380% faster to about 7,000%faster, about 380% faster to about 6,000% faster, about 380% faster toabout 5,000% faster, about 380% faster to about 4,000% faster, about380% faster to about 3,000% faster, about 380% faster to about 2,000%faster, about 380% faster to about 1,000% faster, about 380% faster toabout 500% faster, about 380% faster to about 480% faster, about 380%faster to about 460% faster, about 380% faster to about 440% faster,about 380% faster to about 420% faster, about 380% faster to about 400%faster, about 400% faster to about 10,000% faster, about 400% faster toabout 9,000% faster, about 400% faster to about 8,000% faster, about400% faster to about 7,000% faster, about 400% faster to about 6,000%faster, about 400% faster to about 5,000% faster, about 400% faster toabout 4,000% faster, about 400% faster to about 3,000% faster, about400% faster to about 2,000% faster, about 400% faster to about 1,000%faster, about 400% faster to about 500% faster, about 400% faster toabout 480% faster, about 400% faster to about 460% faster, about 400%faster to about 440% faster, about 400% faster to about 420% faster,about 420% faster to about 10,000% faster, about 420% faster to about9,000% faster, about 420% faster to about 8,000% faster, about 420%faster to about 7,000% faster, about 420% faster to about 6,000% faster,about 420% faster to about 5,000% faster, about 420% faster to about4,000% faster, about 420% faster to about 3,000% faster, about 420%faster to about 2,000% faster, about 420% faster to about 1,000% faster,about 420% faster to about 500% faster, about 420% faster to about 480%faster, about 420% faster to about 460% faster, about 420% faster toabout 440% faster, about 440% faster to about 10,000% faster, about 440%faster to about 9,000% faster, about 440% faster to about 8,000% faster,about 440% faster to about 7,000% faster, about 440% faster to about6,000% faster, about 440% faster to about 5,000% faster, about 440%faster to about 4,000% faster, about 440% faster to about 3,000% faster,about 440% faster to about 2,000% faster, about 440% faster to about1,000% faster, about 440% faster to about 500% faster, about 440% fasterto about 480% faster, about 440% faster to about 460% faster, about 460%faster to about 10,000% faster, about 460% faster to about 9,000%faster, about 460% faster to about 8,000% faster, about 460% faster toabout 7,000% faster, about 460% faster to about 6,000% faster, about460% faster to about 5,000% faster, about 460% faster to about 4,000%faster, about 460% faster to about 3,000% faster, about 460% faster toabout 2,000% faster, about 460% faster to about 1,000% faster, about460% faster to about 500% faster, about 460% faster to about 480%faster, about 480% faster to about 10,000% faster, about 480% faster toabout 9,000% faster, about 480% faster to about 8,000% faster, about480% faster to about 7,000% faster, about 480% faster to about 6,000%faster, about 480% faster to about 5,000% faster, about 480% faster toabout 4,000% faster, about 480% faster to about 3,000% faster, about480% faster to about 2,000% faster, about 480% faster to about 1,000%faster, about 480% faster to about 500% faster, about 500% faster toabout 10,000% faster, about 500% faster to about 9,000% faster, about500% faster to about 8,000% faster, about 500% faster to about 7,000%faster, about 500% faster to about 6,000% faster, about 500% faster toabout 5,000% faster, about 500% faster to about 4,000% faster, about500% faster to about 3,000% faster, about 500% faster to about 2,000%faster, about 500% faster to about 1,000% faster, about 1,000% faster toabout 10,000% faster, about 1,000% faster to about 9,000% faster, about1,000% faster to about 8,000% faster, about 1,000% faster to about7,000% faster, about 1,000% faster to about 6,000% faster, about 1,000%faster to about 5,000% faster, about 1,000% faster to about 4,000%faster, about 1,000% faster to about 3,000% faster, about 1,000% fasterto about 2,000% faster, about 2,000% faster to about 10,000% faster,about 2,000% faster to about 9,000% faster, about 2,000% faster to about8,000% faster, about 2,000% faster to about 7,000% faster, about 2,000%faster to about 6,000% faster, about 2,000% faster to about 5,000%faster, about 2,000% faster to about 4,000% faster, about 2,000% fasterto about 3,000% faster, about 3,000% faster to about 10,000% faster,about 3,000% faster to about 9,000% faster, about 3,000% faster to about8,000% faster, about 3,000% faster to about 7,000% faster, about 3,000%faster to about 6,000% faster, about 3,000% faster to about 5,000%faster, about 3,000% faster to about 4,000% faster, about 4,000% fasterto about 10,000% faster, about 4,000% faster to about 9,000% faster,about 4,000% faster to about 8,000% faster, about 4,000% faster to about7,000% faster, about 4,000% faster to about 6,000% faster, about 4,000%faster to about 5,000% faster, about 5,000% faster to about 10,000%faster, about 5,000% faster to about 9,000% faster, about 5,000% fasterto about 8,000% faster, about 5,000% faster to about 7,000% faster,about 5,000% faster to about 6,000% faster, about 6,000% faster to about10,000% faster, about 6,000% faster to about 9,000% faster, about 6,000%faster to about 8,000% faster, about 6,000% faster to about 7,000%faster, about 7,000% faster to about 10,000% faster, about 7,000% fasterto about 9,000% faster, about 7,000% faster to about 8,000% faster,about 8,000% faster to about 10,000% faster, about 8,000% faster toabout 9,000% faster, or about 9,000% faster to about 10,000% faster)than the dissociation rate at a pH of about 7.0 to about 8.0 (e.g.,about 7.0 to about 7.9, about 7.0 to about 7.8, about 7.0 to about 7.7,about 7.0 to about 7.6, about 7.0 to about 7.5, about 7.0 to about 7.4,about 7.0 to about 7.3, about 7.0 to about 7.2, about 7.0 to about 7.1,about 7.1 to about 8.0, about 7.1 to about 7.9, about 7.1 to about 7.8,about 7.1 to about 7.7, about 7.1 to about 7.6, about 7.1 to about 7.5,about 7.1 to about 7.4, about 7.1 to about 7.3, about 7.1 to about 7.2,about 7.2 to about 8.0, about 7.2 to about 7.9, about 7.2 to about 7.8,about 7.2 to about 7.7, about 7.2 to about 7.6, about 7.2 to about 7.5,about 7.2 to about 7.4, about 7.2 to about 7.3, about 7.3 to about 8.0,about 7.3 to about 7.9, about 7.3 to about 7.8, about 7.3 to about 7.7,about 7.3 to about 7.6, about 7.3 to about 7.5, about 7.3 to about 7.4,about 7.4 to about 8.0, about 7.4 to about 7.9, about 7.4 to about 7.8,about 7.4 to about 7.7, about 7.4 to about 7.6, about 7.4 to about 7.5,about 7.5 to about 8.0, about 7.5 to about 7.9, about 7.5 to about 7.8,about 7.5 to about 7.7, about 7.5 to about 7.6, about 7.6 to about 8.0,about 7.6 to about 7.9, about 7.6 to about 7.8, about 7.6 to about 7.7,about 7.7 to about 8.0, about 7.7 to about 7.9, about 7.7 to about 7.8,about 7.8 to about 8.0, about 7.8 to about 7.9, or about 7.9 to about8.0).

In some embodiments of any of the antigen-binding protein constructs(ABPCs) described herein, the dissociation constant (K_(D)) of the firstantigen-binding domain (and optionally the second antigen-bindingdomain, if present) at a pH of about 4.0 to about 6.5 (e.g., any of thesubranges of this range described herein) is greater (e.g., detectablygreater) (e.g., at least 5% greater, at least 10% greater, at least 15%greater, at least 20% greater, at least 25% greater, at least 30%greater, at least 35% greater, at least 40% greater, at least 45%greater, at least 50% greater, at least 55% greater, at least 60%greater, at least 65% greater, at least 70% greater, at least 80%greater, at least 85% greater, at least 90% greater, at least 95%greater, at least 100% greater, at least 120% greater, at least 140%greater, at least 160% greater, at least 180% greater, at least 200%greater, at least 220% greater, at least 240% greater, at least 260%greater, at least 280% greater, at least 300% greater, at least 320%greater, at least 340% greater, at least 360% greater, at least 380%greater, at least 400% greater, at least 420% greater, at least 440%greater, at least 460% greater, at least 480% greater, at least 500%greater, at least 1,000% greater, at least 2,000% greater, at least3,000% greater, at least 4,000% greater, at least 5,000% greater, atleast 6,000% greater, at least 7,000% greater, at least 8,000% greater,at least 9,000% greater, or at least 10,000% greater, or about 5%greater to about 10,000% greater, about 5% greater to about 9,000%greater, about 5% greater to about 8,000% greater, about 5% greater toabout 7,000% greater, about 5% greater to about 6,000% greater, about 5%greater to about 5,000% greater, about 5% greater to about 4,000%greater, about 5% greater to about 3,000% greater, about 5% greater toabout 2,000% greater, about 5% greater to about 1,000% greater, about 5%greater to about 500% greater, about 5% greater to about 480% greater,about 5% greater to about 460% greater, about 5% greater to about 440%greater, about 5% greater to about 420% greater, about 5% greater toabout 400% greater, about 5% greater to about 380% greater, about 5%greater to about 360% greater, about 5% greater to about 340% greater,about 5% greater to about 320% greater, about 5% greater to about 300%greater, about 5% greater to about 280% greater, about 5% greater toabout 260% greater, about 5% greater to about 240% greater, about 5%greater to about 220% greater, about 5% greater to about 200% greater,about 5% greater to about 180% greater, about 5% greater to about 160%greater, about 5% greater to about 140% greater, about 5% greater toabout 120% greater, about 5% greater to about 100% greater, about 5%greater to about 95% greater, about 5% greater to about 90% greater,about 5% greater to about 85% greater, about 5% greater to about 80%greater, about 5% greater to about 75% greater, about 5% greater toabout 70% greater, about 5% greater to about 65% greater, about 5%greater to about 60% greater, about 5% greater to about 55% greater,about 5% greater to about 50% greater, about 5% greater to about 45%greater, about 5% greater to about 40% greater, about 5% greater toabout 35% greater, about 5% greater to about 30% greater, about 5%greater to about 25% greater, about 5% greater to about 20% greater,about 5% greater to about 15% greater, about 5% greater to about 10%greater, about 10% greater to about 10,000% greater, about 10% greaterto about 9,000% greater, about 10% greater to about 8,000% greater,about 10% greater to about 7,000% greater, about 10% greater to about6,000% greater, about 10% greater to about 5,000% greater, about 10%greater to about 4,000% greater, about 10% greater to about 3,000%greater, about 10% greater to about 2,000% greater, about 10% greater toabout 1,000% greater, about 10% greater to about 500% greater, about 10%greater to about 480% greater, about 10% greater to about 460% greater,about 10% greater to about 440% greater, about 10% greater to about 420%greater, about 10% greater to about 400% greater, about 10% greater toabout 380% greater, about 10% greater to about 360% greater, about 10%greater to about 340% greater, about 10% greater to about 320% greater,about 10% greater to about 300% greater, about 10% greater to about 280%greater, about 10% greater to about 260% greater, about 10% greater toabout 240% greater, about 10% greater to about 220% greater, about 10%greater to about 200% greater, about 10% greater to about 180% greater,about 10% greater to about 160% greater, about 10% greater to about 140%greater, about 10% greater to about 120% greater, about 10% greater toabout 100% greater, about 10% greater to about 95% greater, about 10%greater to about 90% greater, about 10% greater to about 85% greater,about 10% greater to about 80% greater, about 10% greater to about 75%greater, about 10% greater to about 70% greater, about 10% greater toabout 65% greater, about 10% greater to about 60% greater, about 10%greater to about 55% greater, about 10% greater to about 50% greater,about 10% greater to about 45% greater, about 10% greater to about 40%greater, about 10% greater to about 35% greater, about 10% greater toabout 30% greater, about 10% greater to about 25% greater, about 10%greater to about 20% greater, about 10% greater to about 15% greater,about 15% greater to about 10,000% greater, about 15% greater to about9,000% greater, about 15% greater to about 8,000% greater, about 15%greater to about 7,000% greater, about 15% greater to about 6,000%greater, about 15% greater to about 5,000% greater, about 15% greater toabout 4,000% greater, about 15% greater to about 3,000% greater, about15% greater to about 2,000% greater, about 15% greater to about 1,000%greater, about 15% greater to about 500% greater, about 15% greater toabout 480% greater, about 15% greater to about 460% greater, about 15%greater to about 440% greater, about 15% greater to about 420% greater,about 15% greater to about 400% greater, about 15% greater to about 380%greater, about 15% greater to about 360% greater, about 15% greater toabout 340% greater, about 15% greater to about 320% greater, about 15%greater to about 300% greater, about 15% greater to about 280% greater,about 15% greater to about 260% greater, about 15% greater to about 240%greater, about 15% greater to about 220% greater, about 15% greater toabout 200% greater, about 15% greater to about 180% greater, about 15%greater to about 160% greater, about 15% greater to about 140% greater,about 15% greater to about 120% greater, about 15% greater to about 100%greater, about 15% greater to about 95% greater, about 15% greater toabout 90% greater, about 15% greater to about 85% greater, about 15%greater to about 80% greater, about 15% greater to about 75% greater,about 15% greater to about 70% greater, about 15% greater to about 65%greater, about 15% greater to about 60% greater, about 15% greater toabout 55% greater, about 15% greater to about 50% greater, about 15%greater to about 45% greater, about 15% greater to about 40% greater,about 15% greater to about 35% greater, about 15% greater to about 30%greater, about 15% greater to about 25% greater, about 15% greater toabout 20% greater, about 20% greater to about 10,000% greater, about 20%greater to about 9,000% greater, about 20% greater to about 8,000%greater, about 20% greater to about 7,000% greater, about 20% greater toabout 6,000% greater, about 20% greater to about 5,000% greater, about20% greater to about 4,000% greater, about 20% greater to about 3,000%greater, about 20% greater to about 2,000% greater, about 20% greater toabout 1,000% greater, about 20% greater to about 500% greater, about 20%greater to about 480% greater, about 20% greater to about 460% greater,about 20% greater to about 440% greater, about 20% greater to about 420%greater, about 20% greater to about 400% greater, about 20% greater toabout 380% greater, about 20% greater to about 360% greater, about 20%greater to about 340% greater, about 20% greater to about 320% greater,about 20% greater to about 300% greater, about 20% greater to about 280%greater, about 20% greater to about 260% greater, about 20% greater toabout 240% greater, about 20% greater to about 220% greater, about 20%greater to about 200% greater, about 20% greater to about 180% greater,about 20% greater to about 160% greater, about 20% greater to about 140%greater, about 20% greater to about 120% greater, about 20% greater toabout 100% greater, about 20% greater to about 95% greater, about 20%greater to about 90% greater, about 20% greater to about 85% greater,about 20% greater to about 80% greater, about 20% greater to about 75%greater, about 20% greater to about 70% greater, about 20% greater toabout 65% greater, about 20% greater to about 60% greater, about 20%greater to about 55% greater, about 20% greater to about 50% greater,about 20% greater to about 45% greater, about 20% greater to about 40%greater, about 20% greater to about 35% greater, about 20% greater toabout 30% greater, about 20% greater to about 25% greater, about 25%greater to about 10,000% greater, about 25% greater to about 9,000%greater, about 25% greater to about 8,000% greater, about 25% greater toabout 7,000% greater, about 25% greater to about 6,000% greater, about25% greater to about 5,000% greater, about 25% greater to about 4,000%greater, about 25% greater to about 3,000% greater, about 25% greater toabout 2,000% greater, about 25% greater to about 1,000% greater, about25% greater to about 500% greater, about 25% greater to about 480%greater, about 25% greater to about 460% greater, about 25% greater toabout 440% greater, about 25% greater to about 420% greater, about 25%greater to about 400% greater, about 25% greater to about 380% greater,about 25% greater to about 360% greater, about 25% greater to about 340%greater, about 25% greater to about 320% greater, about 25% greater toabout 300% greater, about 25% greater to about 280% greater, about 25%greater to about 260% greater, about 25% greater to about 240% greater,about 25% greater to about 220% greater, about 25% greater to about 200%greater, about 25% greater to about 180% greater, about 25% greater toabout 160% greater, about 25% greater to about 140% greater, about 25%greater to about 120% greater, about 25% greater to about 100% greater,about 25% greater to about 95% greater, about 25% greater to about 90%greater, about 25% greater to about 85% greater, about 25% greater toabout 80% greater, about 25% greater to about 75% greater, about 25%greater to about 70% greater, about 25% greater to about 65% greater,about 25% greater to about 60% greater, about 25% greater to about 55%greater, about 25% greater to about 50% greater, about 25% greater toabout 45% greater, about 25% greater to about 40% greater, about 25%greater to about 35% greater, about 25% greater to about 30% greater,about 30% greater to about 10,000% greater, about 30% greater to about9,000% greater, about 30% greater to about 8,000% greater, about 30%greater to about 7,000% greater, about 30% greater to about 6,000%greater, about 30% greater to about 5,000% greater, about 30% greater toabout 4,000% greater, about 30% greater to about 3,000% greater, about30% greater to about 2,000% greater, about 30% greater to about 1,000%greater, about 30% greater to about 500% greater, about 30% greater toabout 480% greater, about 30% greater to about 460% greater, about 30%greater to about 440% greater, about 30% greater to about 420% greater,about 30% greater to about 400% greater, about 30% greater to about 380%greater, about 30% greater to about 360% greater, about 30% greater toabout 340% greater, about 30% greater to about 320% greater, about 30%greater to about 300% greater, about 30% greater to about 280% greater,about 30% greater to about 260% greater, about 30% greater to about 240%greater, about 30% greater to about 220% greater, about 30% greater toabout 200% greater, about 30% greater to about 180% greater, about 30%greater to about 160% greater, about 30% greater to about 140% greater,about 30% greater to about 120% greater, about 30% greater to about 100%greater, about 30% greater to about 95% greater, about 30% greater toabout 90% greater, about 30% greater to about 85% greater, about 30%greater to about 80% greater, about 30% greater to about 75% greater,about 30% greater to about 70% greater, about 30% greater to about 65%greater, about 30% greater to about 60% greater, about 30% greater toabout 55% greater, about 30% greater to about 50% greater, about 30%greater to about 45% greater, about 30% greater to about 40% greater,about 30% greater to about 35% greater, about 35% greater to about10,000% greater, about 35% greater to about 9,000% greater, about 35%greater to about 8,000% greater, about 35% greater to about 7,000%greater, about 35% greater to about 6,000% greater, about 35% greater toabout 5,000% greater, about 35% greater to about 4,000% greater, about35% greater to about 3,000% greater, about 35% greater to about 2,000%greater, about 35% greater to about 1,000% greater, about 35% greater toabout 500% greater, about 35% greater to about 480% greater, about 35%greater to about 460% greater, about 35% greater to about 440% greater,about 35% greater to about 420% greater, about 35% greater to about 400%greater, about 35% greater to about 380% greater, about 35% greater toabout 360% greater, about 35% greater to about 340% greater, about 35%greater to about 320% greater, about 35% greater to about 300% greater,about 35% greater to about 280% greater, about 35% greater to about 260%greater, about 35% greater to about 240% greater, about 35% greater toabout 220% greater, about 35% greater to about 200% greater, about 35%greater to about 180% greater, about 35% greater to about 160% greater,about 35% greater to about 140% greater, about 35% greater to about 120%greater, about 35% greater to about 100% greater, about 35% greater toabout 95% greater, about 35% greater to about 90% greater, about 35%greater to about 85% greater, about 35% greater to about 80% greater,about 35% greater to about 75% greater, about 35% greater to about 70%greater, about 35% greater to about 65% greater, about 35% greater toabout 60% greater, about 35% greater to about 55% greater, about 35%greater to about 50% greater, about 35% greater to about 45% greater,about 35% greater to about 40% greater, about 40% greater to about10,000% greater, about 40% greater to about 9,000% greater, about 40%greater to about 8,000% greater, about 40% greater to about 7,000%greater, about 40% greater to about 6,000% greater, about 40% greater toabout 5,000% greater, about 40% greater to about 4,000% greater, about40% greater to about 3,000% greater, about 40% greater to about 2,000%greater, about 40% greater to about 1,000% greater, about 40% greater toabout 500% greater, about 40% greater to about 480% greater, about 40%greater to about 460% greater, about 40% greater to about 440% greater,about 40% greater to about 420% greater, about 40% greater to about 400%greater, about 40% greater to about 380% greater, about 40% greater toabout 360% greater, about 40% greater to about 340% greater, about 40%greater to about 320% greater, about 40% greater to about 300% greater,about 40% greater to about 280% greater, about 40% greater to about 260%greater, about 40% greater to about 240% greater, about 40% greater toabout 220% greater, about 40% greater to about 200% greater, about 40%greater to about 180% greater, about 40% greater to about 160% greater,about 40% greater to about 140% greater, about 40% greater to about 120%greater, about 40% greater to about 100% greater, about 40% greater toabout 95% greater, about 40% greater to about 90% greater, about 40%greater to about 85% greater, about 40% greater to about 80% greater,about 40% greater to about 75% greater, about 40% greater to about 70%greater, about 40% greater to about 65% greater, about 40% greater toabout 60% greater, about 40% greater to about 55% greater, about 40%greater to about 50% greater, about 40% greater to about 45% greater,about 45% greater to about 10,000% greater, about 45% greater to about9,000% greater, about 45% greater to about 8,000% greater, about 45%greater to about 7,000% greater, about 45% greater to about 6,000%greater, about 45% greater to about 5,000% greater, about 45% greater toabout 4,000% greater, about 45% greater to about 3,000% greater, about45% greater to about 2,000% greater, about 45% greater to about 1,000%greater, about 45% greater to about 500% greater, about 45% greater toabout 480% greater, about 45% greater to about 460% greater, about 45%greater to about 440% greater, about 45% greater to about 420% greater,about 45% greater to about 400% greater, about 45% greater to about 380%greater, about 45% greater to about 360% greater, about 45% greater toabout 340% greater, about 45% greater to about 320% greater, about 45%greater to about 300% greater, about 45% greater to about 280% greater,about 45% greater to about 260% greater, about 45% greater to about 240%greater, about 45% greater to about 220% greater, about 45% greater toabout 200% greater, about 45% greater to about 180% greater, about 45%greater to about 160% greater, about 45% greater to about 140% greater,about 45% greater to about 120% greater, about 45% greater to about 100%greater, about 45% greater to about 95% greater, about 45% greater toabout 90% greater, about 45% greater to about 85% greater, about 45%greater to about 80% greater, about 45% greater to about 75% greater,about 45% greater to about 70% greater, about 45% greater to about 65%greater, about 45% greater to about 60% greater, about 45% greater toabout 55% greater, about 45% greater to about 50% greater, about 50%greater to about 10,000% greater, about 50% greater to about 9,000%greater, about 50% greater to about 8,000% greater, about 50% greater toabout 7,000% greater, about 50% greater to about 6,000% greater, about50% greater to about 5,000% greater, about 50% greater to about 4,000%greater, about 50% greater to about 3,000% greater, about 50% greater toabout 2,000% greater, about 50% greater to about 1,000% greater, about50% greater to about 500% greater, about 50% greater to about 480%greater, about 50% greater to about 460% greater, about 50% greater toabout 440% greater, about 50% greater to about 420% greater, about 50%greater to about 400% greater, about 50% greater to about 380% greater,about 50% greater to about 360% greater, about 50% greater to about 340%greater, about 50% greater to about 320% greater, about 50% greater toabout 300% greater, about 50% greater to about 280% greater, about 50%greater to about 260% greater, about 50% greater to about 240% greater,about 50% greater to about 220% greater, about 50% greater to about 200%greater, about 50% greater to about 180% greater, about 50% greater toabout 160% greater, about 50% greater to about 140% greater, about 50%greater to about 120% greater, about 50% greater to about 100% greater,about 50% greater to about 95% greater, about 50% greater to about 90%greater, about 50% greater to about 85% greater, about 50% greater toabout 80% greater, about 50% greater to about 75% greater, about 50%greater to about 70% greater, about 50% greater to about 65% greater,about 50% greater to about 60% greater, about 50% greater to about 55%greater, about 55% greater to about 10,000% greater, about 55% greaterto about 9,000% greater, about 55% greater to about 8,000% greater,about 55% greater to about 7,000% greater, about 55% greater to about6,000% greater, about 55% greater to about 5,000% greater, about 55%greater to about 4,000% greater, about 55% greater to about 3,000%greater, about 55% greater to about 2,000% greater, about 55% greater toabout 1,000% greater, about 55% greater to about 500% greater, about 55%greater to about 480% greater, about 55% greater to about 460% greater,about 55% greater to about 440% greater, about 55% greater to about 420%greater, about 55% greater to about 400% greater, about 55% greater toabout 380% greater, about 55% greater to about 360% greater, about 55%greater to about 340% greater, about 55% greater to about 320% greater,about 55% greater to about 300% greater, about 55% greater to about 280%greater, about 55% greater to about 260% greater, about 55% greater toabout 240% greater, about 55% greater to about 220% greater, about 55%greater to about 200% greater, about 55% greater to about 180% greater,about 55% greater to about 160% greater, about 55% greater to about 140%greater, about 55% greater to about 120% greater, about 55% greater toabout 100% greater, about 55% greater to about 95% greater, about 55%greater to about 90% greater, about 55% greater to about 85% greater,about 55% greater to about 80% greater, about 55% greater to about 75%greater, about 55% greater to about 70% greater, about 55% greater toabout 65% greater, about 55% greater to about 60% greater, about 60%greater to about 10,000% greater, about 60% greater to about 9,000%greater, about 60% greater to about 8,000% greater, about 60% greater toabout 7,000% greater, about 60% greater to about 6,000% greater, about60% greater to about 5,000% greater, about 60% greater to about 4,000%greater, about 60% greater to about 3,000% greater, about 60% greater toabout 2,000% greater, about 60% greater to about 1,000% greater, about60% greater to about 500% greater, about 60% greater to about 480%greater, about 60% greater to about 460% greater, about 60% greater toabout 440% greater, about 60% greater to about 420% greater, about 60%greater to about 400% greater, about 60% greater to about 380% greater,about 60% greater to about 360% greater, about 60% greater to about 340%greater, about 60% greater to about 320% greater, about 60% greater toabout 300% greater, about 60% greater to about 280% greater, about 60%greater to about 260% greater, about 60% greater to about 240% greater,about 60% greater to about 220% greater, about 60% greater to about 200%greater, about 60% greater to about 180% greater, about 60% greater toabout 160% greater, about 60% greater to about 140% greater, about 60%greater to about 120% greater, about 60% greater to about 100% greater,about 60% greater to about 95% greater, about 60% greater to about 90%greater, about 60% greater to about 85% greater, about 60% greater toabout 80% greater, about 60% greater to about 75% greater, about 60%greater to about 70% greater, about 60% greater to about 65% greater,about 65% greater to about 10,000% greater, about 65% greater to about9,000% greater, about 65% greater to about 8,000% greater, about 65%greater to about 7,000% greater, about 65% greater to about 6,000%greater, about 65% greater to about 5,000% greater, about 65% greater toabout 4,000% greater, about 65% greater to about 3,000% greater, about65% greater to about 2,000% greater, about 65% greater to about 1,000%greater, about 65% greater to about 500% greater, about 65% greater toabout 480% greater, about 65% greater to about 460% greater, about 65%greater to about 440% greater, about 65% greater to about 420% greater,about 65% greater to about 400% greater, about 65% greater to about 380%greater, about 65% greater to about 360% greater, about 65% greater toabout 340% greater, about 65% greater to about 320% greater, about 65%greater to about 300% greater, about 65% greater to about 280% greater,about 65% greater to about 260% greater, about 65% greater to about 240%greater, about 65% greater to about 220% greater, about 65% greater toabout 200% greater, about 65% greater to about 180% greater, about 65%greater to about 160% greater, about 65% greater to about 140% greater,about 65% greater to about 120% greater, about 65% greater to about 100%greater, about 65% greater to about 95% greater, about 65% greater toabout 90% greater, about 65% greater to about 85% greater, about 65%greater to about 80% greater, about 65% greater to about 75% greater,about 65% greater to about 70% greater, about 70% greater to about10,000% greater, about 70% greater to about 9,000% greater, about 70%greater to about 8,000% greater, about 70% greater to about 7,000%greater, about 70% greater to about 6.000% greater, about 70% greater toabout 5,000% greater, about 70% greater to about 4,000% greater, about70% greater to about 3,000% greater, about 70% greater to about 2,000%greater, about 70% greater to about 1,000% greater, about 70% greater toabout 500% greater, about 70% greater to about 480% greater, about 70%greater to about 460% greater, about 70% greater to about 440% greater,about 70% greater to about 420% greater, about 70% greater to about 400%greater, about 70% greater to about 380% greater, about 70% greater toabout 360% greater, about 70% greater to about 340% greater, about 70%greater to about 320% greater, about 70% greater to about 300% greater,about 70% greater to about 280% greater, about 70% greater to about 260%greater, about 70% greater to about 240% greater, about 70% greater toabout 220% greater, about 70% greater to about 200% greater, about 70%greater to about 180% greater, about 70% greater to about 160% greater,about 70% greater to about 140% greater, about 70% greater to about 120%greater, about 70% greater to about 100% greater, about 70% greater toabout 95% greater, about 70% greater to about 90% greater, about 70%greater to about 85% greater, about 70% greater to about 80% greater,about 70% greater to about 75% greater, about 75% greater to about10,000% greater, about 75% greater to about 9,000% greater, about 75%greater to about 8,000% greater, about 75% greater to about 7,000%greater, about 75% greater to about 6,000% greater, about 75% greater toabout 5,000% greater, about 75% greater to about 4,000% greater, about75% greater to about 3,000% greater, about 75% greater to about 2,000%greater, about 75% greater to about 1,000% greater, about 75% greater toabout 500% greater, about 75% greater to about 480% greater, about 75%greater to about 460% greater, about 75% greater to about 440% greater,about 75% greater to about 420% greater, about 75% greater to about 400%greater, about 75% greater to about 380% greater, about 75% greater toabout 360% greater, about 75% greater to about 340% greater, about 75%greater to about 320% greater, about 75% greater to about 300% greater,about 75% greater to about 280% greater, about 75% greater to about 260%greater, about 75% greater to about 240% greater, about 75% greater toabout 220% greater, about 75% greater to about 200% greater, about 75%greater to about 180% greater, about 75% greater to about 160% greater,about 75% greater to about 140% greater, about 75% greater to about 120%greater, about 75% greater to about 100% greater, about 75% greater toabout 95% greater, about 75% greater to about 90% greater, about 75%greater to about 85% greater, about 75% greater to about 80% greater,about 80% greater to about 10,000% greater, about 80% greater to about9,000% greater, about 80% greater to about 8,000% greater, about 80%greater to about 7,000% greater, about 80% greater to about 6,000%greater, about 80% greater to about 5,000% greater, about 80% greater toabout 4,000% greater, about 80% greater to about 3,000% greater, about80% greater to about 2,000% greater, about 80% greater to about 1,000%greater, about 80% greater to about 500% greater, about 80% greater toabout 480% greater, about 80% greater to about 460% greater, about 80%greater to about 440% greater, about 80% greater to about 420% greater,about 80% greater to about 400% greater, about 80% greater to about 380%greater, about 80% greater to about 360% greater, about 80% greater toabout 340% greater, about 80% greater to about 320% greater, about 80%greater to about 300% greater, about 80% greater to about 280% greater,about 80% greater to about 260% greater, about 80% greater to about 240%greater, about 80% greater to about 220% greater, about 80% greater toabout 200% greater, about 80% greater to about 180% greater, about 80%greater to about 160% greater, about 80% greater to about 140% greater,about 80% greater to about 120% greater, about 80% greater to about 100%greater, about 80% greater to about 95% greater, about 80% greater toabout 90% greater, about 80% greater to about 85% greater, about 85%greater to about 10,000% greater, about 85% greater to about 9,000%greater, about 85% greater to about 8,000% greater, about 85% greater toabout 7,000% greater, about 85% greater to about 6,000% greater, about85% greater to about 5,000% greater, about 85% greater to about 4,000%greater, about 85% greater to about 3,000% greater, about 85% greater toabout 2,000% greater, about 85% greater to about 1,000% greater, about85% greater to about 500% greater, about 85% greater to about 480%greater, about 85% greater to about 460% greater, about 85% greater toabout 440% greater, about 85% greater to about 420% greater, about 85%greater to about 400% greater, about 85% greater to about 380% greater,about 85% greater to about 360% greater, about 85% greater to about 340%greater, about 85% greater to about 320% greater, about 85% greater toabout 300% greater, about 85% greater to about 280% greater, about 85%greater to about 260% greater, about 85% greater to about 240% greater,about 85% greater to about 220% greater, about 85% greater to about 200%greater, about 85% greater to about 180% greater, about 85% greater toabout 160% greater, about 85% greater to about 140% greater, about 85%greater to about 120% greater, about 85% greater to about 100% greater,about 85% greater to about 95% greater, about 85% greater to about 90%greater, about 90% greater to about 10,000% greater, about 90% greaterto about 9,000% greater, about 90% greater to about 8,000% greater,about 90% greater to about 7,000% greater, about 90% greater to about6,000% greater, about 90% greater to about 5,000% greater, about 90%greater to about 4,000% greater, about 90% greater to about 3,000%greater, about 90% greater to about 2,000% greater, about 90% greater toabout 1,000% greater, about 90% greater to about 500% greater, about 90%greater to about 480% greater, about 90% greater to about 460% greater,about 90% greater to about 440% greater, about 90% greater to about 420%greater, about 90% greater to about 400% greater, about 90% greater toabout 380% greater, about 90% greater to about 360% greater, about 90%greater to about 340% greater, about 90% greater to about 320% greater,about 90% greater to about 300% greater, about 90% greater to about 280%greater, about 90% greater to about 260% greater, about 90% greater toabout 240% greater, about 90% greater to about 220% greater, about 90%greater to about 200% greater, about 90% greater to about 180% greater,about 90% greater to about 160% greater, about 90% greater to about 140%greater, about 90% greater to about 120% greater, about 90% greater toabout 100% greater, about 90% greater to about 95% greater, about 95%greater to about 10,000% greater, about 95% greater to about 9,000%greater, about 95% greater to about 8,000% greater, about 95% greater toabout 7,000% greater, about 95% greater to about 6,000% greater, about95% greater to about 5,000% greater, about 95% greater to about 4,000%greater, about 95% greater to about 3,000% greater, about 95% greater toabout 2,000% greater, about 95% greater to about 1,000% greater, about95% greater to about 500% greater, about 95% greater to about 480%greater, about 95% greater to about 460% greater, about 95% greater toabout 440% greater, about 95% greater to about 420% greater, about 95%greater to about 400% greater, about 95% greater to about 380% greater,about 95% greater to about 360% greater, about 95% greater to about 340%greater, about 95% greater to about 320% greater, about 95% greater toabout 300% greater, about 95% greater to about 280% greater, about 95%greater to about 260% greater, about 95% greater to about 240% greater,about 95% greater to about 220% greater, about 95% greater to about 200%greater, about 95% greater to about 180% greater, about 95% greater toabout 160% greater, about 95% greater to about 140% greater, about 95%greater to about 120% greater, about 95% greater to about 100% greater,about 100% greater to about 10,000% greater, about 100% greater to about9,000% greater, about 100% greater to about 8,000% greater, about 100%greater to about 7,000% greater, about 100% greater to about 6,000%greater, about 100% greater to about 5,000% greater, about 100% greaterto about 4,000% greater, about 100% greater to about 3,000% greater,about 100% greater to about 2,000% greater, about 100% greater to about1,000% greater, about 100% greater to about 500% greater, about 100%greater to about 480% greater, about 100% greater to about 460% greater,about 100% greater to about 440% greater, about 100% greater to about420% greater, about 100% greater to about 400% greater, about 100%greater to about 380% greater, about 100% greater to about 360% greater,about 100% greater to about 340% greater, about 100% greater to about320% greater, about 100% greater to about 300% greater, about 100%greater to about 280% greater, about 100% greater to about 260% greater,about 100% greater to about 240% greater, about 100% greater to about220% greater, about 100% greater to about 200% greater, about 100%greater to about 180% greater, about 100% greater to about 160% greater,about 100% greater to about 140% greater, about 100% greater to about120% greater, about 120% greater to about 10,000% greater, about 120%greater to about 9,000% greater, about 120% greater to about 8,000%greater, about 120% greater to about 7,000% greater, about 120% greaterto about 6,000% greater, about 120% greater to about 5,000% greater,about 120% greater to about 4,000% greater, about 120% greater to about3,000% greater, about 120% greater to about 2,000% greater, about 120%greater to about 1,000% greater, about 120% greater to about 500%greater, about 120% greater to about 480% greater, about 120% greater toabout 460% greater, about 120% greater to about 440% greater, about 120%greater to about 420% greater, about 120% greater to about 400% greater,about 120% greater to about 380% greater, about 120% greater to about360% greater, about 120% greater to about 340% greater, about 120%greater to about 320% greater, about 120% greater to about 300% greater,about 120% greater to about 280% greater, about 120% greater to about260% greater, about 120% greater to about 240% greater, about 120%greater to about 220% greater, about 120% greater to about 200% greater,about 120% greater to about 180% greater, about 120% greater to about160% greater, about 120% greater to about 140% greater, about 140%greater to about 10,000% greater, about 140% greater to about 9,000%greater, about 140% greater to about 8,000% greater, about 140% greaterto about 7,000% greater, about 140% greater to about 6,000% greater,about 140% greater to about 5,000% greater, about 140% greater to about4,000% greater, about 140% greater to about 3,000% greater, about 140%greater to about 2,000% greater, about 140% greater to about 1,000%greater, about 140% greater to about 500% greater, about 140% greater toabout 480% greater, about 140% greater to about 460% greater, about 140%greater to about 440% greater, about 140% greater to about 420% greater,about 140% greater to about 400% greater, about 140% greater to about380% greater, about 140% greater to about 360% greater, about 140%greater to about 340% greater, about 140% greater to about 320% greater,about 140% greater to about 300% greater, about 140% greater to about280% greater, about 140% greater to about 260% greater, about 140%greater to about 240% greater, about 140% greater to about 220% greater,about 140% greater to about 200% greater, about 140% greater to about180% greater, about 140% greater to about 160% greater, about 160%greater to about 10,000% greater, about 160% greater to about 9,000%greater, about 160% greater to about 8,000% greater, about 160% greaterto about 7,000% greater, about 160% greater to about 6,000% greater,about 160% greater to about 5,000% greater, about 160% greater to about4,000% greater, about 160% greater to about 3,000% greater, about 160%greater to about 2,000% greater, about 160% greater to about 1,000%greater, about 160% greater to about 500% greater, about 160% greater toabout 480% greater, about 160% greater to about 460% greater, about 160%greater to about 440% greater, about 160% greater to about 420% greater,about 160% greater to about 400% greater, about 160% greater to about380% greater, about 160% greater to about 360% greater, about 160%greater to about 340% greater, about 160% greater to about 320% greater,about 160% greater to about 300% greater, about 160% greater to about280% greater, about 160% greater to about 260% greater, about 160%greater to about 240% greater, about 160% greater to about 220% greater,about 160% greater to about 200% greater, about 160% greater to about180% greater, about 180% greater to about 10,000% greater, about 180%greater to about 9,000% greater, about 180% greater to about 8,000%greater, about 180% greater to about 7,000% greater, about 180% greaterto about 6,000% greater, about 180% greater to about 5,000% greater,about 180% greater to about 4,000% greater, about 180% greater to about3,000% greater, about 180% greater to about 2,000% greater, about 180%greater to about 1,000% greater, about 180% greater to about 500%greater, about 180% greater to about 480% greater, about 180% greater toabout 460% greater, about 180% greater to about 440% greater, about 180%greater to about 420% greater, about 180% greater to about 400% greater,about 180% greater to about 380% greater, about 180% greater to about360% greater, about 180% greater to about 340% greater, about 180%greater to about 320% greater, about 180% greater to about 300% greater,about 180% greater to about 280% greater, about 180% greater to about260% greater, about 180% greater to about 240% greater, about 180%greater to about 220% greater, about 180% greater to about 200% greater,about 200% greater to about 10,000% greater, about 200% greater to about9,000% greater, about 200% greater to about 8,000% greater, about 200%greater to about 7,000% greater, about 200% greater to about 6,000%greater, about 200% greater to about 5,000% greater, about 200% greaterto about 4,000% greater, about 200% greater to about 3,000% greater,about 200% greater to about 2,000% greater, about 200% greater to about1,000% greater, about 200% greater to about 500% greater, about 200%greater to about 480% greater, about 200% greater to about 460% greater,about 200% greater to about 440% greater, about 200% greater to about420% greater, about 200% greater to about 400% greater, about 200%greater to about 380% greater, about 200% greater to about 360% greater,about 200% greater to about 340% greater, about 200% greater to about320% greater, about 200% greater to about 300% greater, about 200%greater to about 280% greater, about 200% greater to about 260% greater,about 200% greater to about 240% greater, about 200% greater to about220% greater, about 220% greater to about 10,000% greater, about 220%greater to about 9,000% greater, about 220% greater to about 8,000%greater, about 220% greater to about 7,000% greater, about 220% greaterto about 6,000% greater, about 220% greater to about 5,000% greater,about 220% greater to about 4,000% greater, about 220% greater to about3,000% greater, about 220% greater to about 2,000% greater, about 220%greater to about 1,000% greater, about 220% greater to about 500%greater, about 220% greater to about 480% greater, about 220% greater toabout 460% greater, about 220% greater to about 440% greater, about 220%greater to about 420% greater, about 220% greater to about 400% greater,about 220% greater to about 380% greater, about 220% greater to about360% greater, about 220% greater to about 340% greater, about 220%greater to about 320% greater, about 220% greater to about 300% greater,about 220% greater to about 280% greater, about 220% greater to about260% greater, about 220% greater to about 240% greater, about 240%greater to about 10,000% greater, about 240% greater to about 9,000%greater, about 240% greater to about 8,000% greater, about 240% greaterto about 7,000% greater, about 240% greater to about 6,000% greater,about 240% greater to about 5,000% greater, about 240% greater to about4,000% greater, about 240% greater to about 3,000% greater, about 240%greater to about 2,000% greater, about 240% greater to about 1,000%greater, about 240% greater to about 500% greater, about 240% greater toabout 480% greater, about 240% greater to about 460% greater, about 240%greater to about 440% greater, about 240% greater to about 420% greater,about 240% greater to about 400% greater, about 240% greater to about380% greater, about 240% greater to about 360% greater, about 240%greater to about 340% greater, about 240% greater to about 320% greater,about 240% greater to about 300% greater, about 240% greater to about280% greater, about 240% greater to about 260% greater, about 260%greater to about 10,000% greater, about 260% greater to about 9,000%greater, about 260% greater to about 8,000% greater, about 260% greaterto about 7,000% greater, about 260% greater to about 6,000% greater,about 260% greater to about 5,000% greater, about 260% greater to about4,000% greater, about 260% greater to about 3,000% greater, about 260%greater to about 2,000% greater, about 260% greater to about 1,000%greater, about 260% greater to about 500% greater, about 260% greater toabout 480% greater, about 260% greater to about 460% greater, about 260%greater to about 440% greater, about 260% greater to about 420% greater,about 260% greater to about 400% greater, about 260% greater to about380% greater, about 260% greater to about 360% greater, about 260%greater to about 340% greater, about 260% greater to about 320% greater,about 260% greater to about 300% greater, about 260% greater to about280% greater, about 280% greater to about 10,000% greater, about 280%greater to about 9,000% greater, about 280% greater to about 8,000%greater, about 280% greater to about 7,000% greater, about 280% greaterto about 6,000% greater, about 280% greater to about 5,000% greater,about 280% greater to about 4,000% greater, about 280% greater to about3,000% greater, about 280% greater to about 2,000% greater, about 280%greater to about 1,000% greater, about 280% greater to about 500%greater, about 280% greater to about 480% greater, about 280% greater toabout 460% greater, about 280% greater to about 440% greater, about 280%greater to about 420% greater, about 280% greater to about 400% greater,about 280% greater to about 380% greater, about 280% greater to about360% greater, about 280% greater to about 340% greater, about 280%greater to about 320% greater, about 280% greater to about 300% greater,about 300% greater to about 10,000% greater, about 300% greater to about9,000% greater, about 300% greater to about 8,000% greater, about 300%greater to about 7,000% greater, about 300% greater to about 6,000%greater, about 300% greater to about 5,000% greater, about 300% greaterto about 4,000% greater, about 300% greater to about 3,000% greater,about 300% greater to about 2,000% greater, about 300% greater to about1,000% greater, about 300% greater to about 500% greater, about 300%greater to about 480% greater, about 300% greater to about 460% greater,about 300% greater to about 440% greater, about 300% greater to about420% greater, about 300% greater to about 400% greater, about 300%greater to about 380% greater, about 300% greater to about 360% greater,about 300% greater to about 340% greater, about 300% greater to about320% greater, about 320% greater to about 10,000% greater, about 320%greater to about 9,000% greater, about 320% greater to about 8,000%greater, about 320% greater to about 7,000% greater, about 320% greaterto about 6,000% greater, about 320% greater to about 5,000% greater,about 320% greater to about 4,000% greater, about 320% greater to about3,000% greater, about 320% greater to about 2,000% greater, about 320%greater to about 1,000% greater, about 320% greater to about 500%greater, about 320% greater to about 480% greater, about 320% greater toabout 460% greater, about 320% greater to about 440% greater, about 320%greater to about 420% greater, about 320% greater to about 400% greater,about 320% greater to about 380% greater, about 320% greater to about360% greater, about 320% greater to about 340% greater, about 340%greater to about 10,000% greater, about 340% greater to about 9,000%greater, about 340% greater to about 8,000% greater, about 340% greaterto about 7,000% greater, about 340% greater to about 6,000% greater,about 340% greater to about 5,000% greater, about 340% greater to about4,000% greater, about 340% greater to about 3,000% greater, about 340%greater to about 2,000% greater, about 340% greater to about 1,000%greater, about 340% greater to about 500% greater, about 340% greater toabout 480% greater, about 340% greater to about 460% greater, about 340%greater to about 440% greater, about 340% greater to about 420% greater,about 340% greater to about 400% greater, about 340% greater to about380% greater, about 340% greater to about 360% greater, about 360%greater to about 10,000% greater, about 360% greater to about 9,000%greater, about 360% greater to about 8,000% greater, about 360% greaterto about 7,000% greater, about 360% greater to about 6,000% greater,about 360% greater to about 5,000% greater, about 360% greater to about4,000% greater, about 360% greater to about 3,000% greater, about 360%greater to about 2,000% greater, about 360% greater to about 1,000%greater, about 360% greater to about 500% greater, about 360% greater toabout 480% greater, about 360% greater to about 460% greater, about 360%greater to about 440% greater, about 360% greater to about 420% greater,about 360% greater to about 400% greater, about 360% greater to about380% greater, about 380% greater to about 10,000% greater, about 380%greater to about 9,000% greater, about 380% greater to about 8,000%greater, about 380% greater to about 7,000% greater, about 380% greaterto about 6,000% greater, about 380% greater to about 5,000% greater,about 380% greater to about 4,000% greater, about 380% greater to about3,000% greater, about 380% greater to about 2,000% greater, about 380%greater to about 1,000% greater, about 380% greater to about 500%greater, about 380% greater to about 480% greater, about 380% greater toabout 460% greater, about 380% greater to about 440% greater, about 380%greater to about 420% greater, about 380% greater to about 400% greater,about 400% greater to about 10,000% greater, about 400% greater to about9,000% greater, about 400% greater to about 8,000% greater, about 400%greater to about 7,000% greater, about 400% greater to about 6,000%greater, about 400% greater to about 5,000% greater, about 400% greaterto about 4,000% greater, about 400% greater to about 3,000% greater,about 400% greater to about 2,000% greater, about 400% greater to about1,000% greater, about 400% greater to about 500% greater, about 400%greater to about 480% greater, about 400% greater to about 460% greater,about 400% greater to about 440% greater, about 400% greater to about420% greater, about 420% greater to about 10,000% greater, about 420%greater to about 9,000% greater, about 420% greater to about 8,000%greater, about 420% greater to about 7,000% greater, about 420% greaterto about 6,000% greater, about 420% greater to about 5,000% greater,about 420% greater to about 4,000% greater, about 420% greater to about3,000% greater, about 420% greater to about 2,000% greater, about 420%greater to about 1,000% greater, about 420% greater to about 500%greater, about 420% greater to about 480% greater, about 420% greater toabout 460% greater, about 420% greater to about 440% greater, about 440%greater to about 10,000% greater, about 440% greater to about 9,000%greater, about 440% greater to about 8,000% greater, about 440% greaterto about 7,000% greater, about 440% greater to about 6,000% greater,about 440% greater to about 5,000% greater, about 440% greater to about4,000% greater, about 440% greater to about 3,000% greater, about 440%greater to about 2,000% greater, about 440% greater to about 1,000%greater, about 440% greater to about 500% greater, about 440% greater toabout 480% greater, about 440% greater to about 460% greater, about 460%greater to about 10,000% greater, about 460% greater to about 9,000%greater, about 460% greater to about 8,000% greater, about 460% greaterto about 7,000% greater, about 460% greater to about 6,000% greater,about 460% greater to about 5,000% greater, about 460% greater to about4,000% greater, about 460% greater to about 3,000% greater, about 460%greater to about 2,000% greater, about 460% greater to about 1,000%greater, about 460% greater to about 500% greater, about 460% greater toabout 480% greater, about 480% greater to about 10,000% greater, about480% greater to about 9,000% greater, about 480% greater to about 8,000%greater, about 480% greater to about 7,000% greater, about 480% greaterto about 6,000% greater, about 480% greater to about 5,000% greater,about 480% greater to about 4,000% greater, about 480% greater to about3,000% greater, about 480% greater to about 2,000% greater, about 480%greater to about 1,000% greater, about 480% greater to about 500%greater, about 500% greater to about 10,000% greater, about 500% greaterto about 9,000% greater, about 500% greater to about 8,000% greater,about 500% greater to about 7,000% greater, about 500% greater to about6,000% greater, about 500% greater to about 5,000% greater, about 500%greater to about 4,000% greater, about 500% greater to about 3,000%greater, about 500% greater to about 2,000% greater, about 500% greaterto about 1,000% greater, about 1,000% greater to about 10,000% greater,about 1,000% greater to about 9,000% greater, about 1,000% greater toabout 8,000% greater, about 1,000% greater to about 7,000% greater,about 1,000% greater to about 6,000% greater, about 1,000% greater toabout 5,000% greater, about 1,000% greater to about 4,000% greater,about 1,000% greater to about 3,000% greater, about 1,000% greater toabout 2,000% greater, about 2,000% greater to about 10,000% greater,about 2,000% greater to about 9,000% greater, about 2,000% greater toabout 8,000% greater, about 2,000% greater to about 7,000% greater,about 2,000% greater to about 6,000% greater, about 2,000% greater toabout 5,000% greater, about 2,000% greater to about 4,000% greater,about 2,000% greater to about 3,000% greater, about 3,000% greater toabout 10,000% greater, about 3,000% greater to about 9,000% greater,about 3,000% greater to about 8,000% greater, about 3,000% greater toabout 7,000% greater, about 3,000% greater to about 6,000% greater,about 3,000% greater to about 5,000% greater, about 3,000% greater toabout 4,000% greater, about 4,000% greater to about 10,000% greater,about 4,000% greater to about 9,000% greater, about 4,000% greater toabout 8,000% greater, about 4,000% greater to about 7,000% greater,about 4,000% greater to about 6,000% greater, about 4,000% greater toabout 5,000% greater, about 5,000% greater to about 10,000% greater,about 5,000% greater to about 9,000% greater, about 5,000% greater toabout 8,000% greater, about 5,000% greater to about 7,000% greater,about 5,000% greater to about 6,000% greater, about 6,000% greater toabout 10,000% greater, about 6,000% greater to about 9,000% greater,about 6,000% greater to about 8,000% greater, about 6,000% greater toabout 7,000% greater, about 7,000% greater to about 10,000% greater,about 7,000% greater to about 9,000% greater, about 7,000% greater toabout 8,000% greater, about 8,000% greater to about 10,000% greater,about 8,000% greater to about 9,000% greater, or about 9,000% greater toabout 10,000% greater) than the K_(D) at a pH of about 7.0 to about 8.0(e.g., any of the subranges of this range described herein).

In some embodiments of any of the antigen-binding protein constructs(ABPCs) described herein, the dissociation rate of the firstantigen-binding domain (and optionally the second antigen-bindingdomain, if present) at a pH of about 4.0 to about 6.5 (e.g., any of thesubranges of this range described herein) is faster (e.g., at least0.2-fold faster, at least 0.3-fold, at least 0.4-fold, at least0.5-fold, at least 0.6-fold, at least 0.7-fold, at least 0.8-fold, atleast 0.9-fold, at least 1.0-fold, at least 1.5-fold, at least 2.0-fold,at least 2.5-fold, at least 3.0 fold, at least 3.5-fold, at least4.0-fold, at least 4.5-fold, at least 5.0-fold, at least 5.5-fold, atleast 6.0-fold, at least 6.5-fold, at least 7.0-fold, at least 7.5-fold,at least 8.0-fold, at least 8.5-fold, at least 9.0-fold, at least9.5-fold, at least 10.0-fold, at least 10.5-fold, at least 11.0-fold, atleast 11.5-fold, at least 12.0-fold, at least 12.5-fold, at least13.0-fold, at least 13.5-fold, at least 14.0-fold, at least 14.5-fold,at least 15.0-fold, at least 15.5-fold, at least 16.0-fold, at least16.5-fold, at least 17.0-fold, at least 17.5-fold, at least 18.0-fold,at least 18.5-fold, at least 19.0-fold, at least 19.5-fold, at least20-fold, at least 25-fold, at least 30-fold, at least 35-fold, at least40-fold, at least 45-fold, at least 50-fold, at least 55-fold, at least60-fold, at least 65-fold, at least 70-fold, at least 75-fold, at least80-fold, at least 85-fold, at least 90-fold, at least 95-fold, or atleast 100-fold faster or about 0.2-fold to about 100-fold faster, about0.2-fold to about 90-fold faster, about 0.2-fold to about 80-foldfaster, about 0.2-fold to about 70-fold faster, about 0.2-fold to about60-fold faster, about 0.2-fold to about 50-fold faster, about 0.2-foldto about 40-fold faster, about 0.2-fold to about 30-fold faster, about0.2-fold to about 20-fold faster, about 0.2-fold to about 15-foldfaster, about 0.2-fold to about 10-fold faster, about 0.2-fold to about5-fold, about 0.2-fold to about 2-fold faster, about 0.2-fold to about1-fold faster, about 0.2-fold to about 0.5-fold faster, about 0.5-foldto about 100-fold faster, about 0.5-fold to about 90-fold faster, about0.5-fold to about 80-fold faster, about 0.5-fold to about 70-foldfaster, about 0.5-fold to about 60-fold faster, about 0.5-fold to about50-fold faster, about 0.5-fold to about 40-fold faster, about 0.5-foldto about 30-fold faster, about 0.5-fold to about 20-fold faster, about0.5-fold to about 15-fold faster, about 0.5-fold to about 10-foldfaster, about 0.5-fold to about 5-fold, about 0.5-fold to about 2-foldfaster, about 0.5-fold to about 1-fold faster, about 1-fold to about100-fold faster, about 1-fold to about 90-fold faster, about 1-fold toabout 80-fold faster, about 1-fold to about 70-fold faster; about 1-foldto about 60-fold faster, about 1-fold to about 50-fold faster, about1-fold to about 40-fold faster, about 1-fold to about 30-fold faster,about 1-fold to about 20-fold faster, about 1-fold to about 15-foldfaster, about 1-fold to about 10-fold faster, about 1-fold to about5-fold, about 1-fold to about 2-fold faster, about 2-fold to about100-fold faster, about 2-fold to about 90-fold faster, about 2-fold toabout 80-fold faster, about 2-fold to about 70-fold faster, about 2-foldto about 60-fold faster, about 2-fold to about 50-fold faster, about2-fold to about 40-fold faster, about 2-fold to about 30-fold faster,about 2-fold to about 20-fold faster, about 2-fold to about 15-foldfaster, about 2-fold to about 10-fold faster, about 2-fold to about5-fold, about 5-fold to about 100-fold faster, about 5-fold to about90-fold faster, about 5-fold to about 80-fold faster, about 5-fold toabout 70-fold faster, about 5-fold to about 60-fold faster, about 5-foldto about 50-fold faster, about 5-fold to about 40-fold faster, about5-fold to about 30-fold faster, about 5-fold to about 20-fold faster,about 5-fold to about 15-fold faster, about 5-fold to about 10-foldfaster, about 10-fold to about 100-fold faster, about 10-fold to about90-fold faster, about 10-fold to about 80-fold faster, about 10-fold toabout 70-fold faster, about 10-fold to about 60-fold faster, about10-fold to about 50-fold faster, about 10-fold to about 40-fold faster,about 10-fold to about 30-fold faster, about 10-fold to about 20-foldfaster, about 10-fold to about 15-fold faster, about 15-fold to about100-fold faster, about 15-fold to about 90-fold faster, about 15-fold toabout 80-fold faster, about 15-fold to about 70-fold faster, about15-fold to about 60-fold faster, about 15-fold to about 50-fold faster,about 15-fold to about 40-fold faster, about 15-fold to about 30-foldfaster, about 15-fold to about 20-fold faster, about 20-fold to about100-fold faster, about 20-fold to about 90-fold faster, about 20-fold toabout 80-fold faster, about 20-fold to about 70-fold faster, about20-fold to about 60-fold faster, about 20-fold to about 50-fold faster,about 20-fold to about 40-fold faster, about 20-fold to about 30-foldfaster, about 30-fold to about 100-fold faster, about 30-fold to about90-fold faster, about 30-fold to about 80-fold faster, about 30-fold toabout 70-fold faster, about 30-fold to about 60-fold faster, about30-fold to about 50-fold faster, about 30-fold to about 40-fold faster,about 40-fold to about 100-fold faster, about 40-fold to about 90-foldfaster, about 40-fold to about 80-fold faster, about 40-fold to about70-fold faster, about 40-fold to about 60-fold faster, about 40-fold toabout 50-fold faster, about 50-fold to about 100-fold faster, about50-fold to about 90-fold faster, about 50-fold to about 80-fold faster,about 50-fold to about 70-fold faster, about 50-fold to about 60-foldfaster, about 60-fold to about 100-fold faster, about 60-fold to about90-fold faster, about 60-fold to about 80-fold faster, about 60-fold toabout 70-fold faster, about 70-fold to about 100-fold faster, about70-fold to about 90-fold faster, about 70-fold to about 80-fold faster,about 80-fold to about 100-fold faster, about 80-fold to about 90-foldfaster, or about 90-fold to about 100-fold faster) than the dissociationrate at a pH of about 7.0 to about 8.0 (e.g., or any of the subranges ofthis range described herein).

In some embodiments of any of the antigen-binding protein constructs(ABPCs) described herein, the dissociation constant (K_(D)) of the firstantigen-binding domain (and optionally the second antigen-bindingdomain, if present) at a pH of about 4.0 to about 6.5 (e.g., any of thesubranges of this range described herein) is greater (e.g., detectablygreater) (e.g., at least 0.2-fold greater, at least 0.3-fold, at least0.4-fold, at least 0.5-fold, at least 0.6-fold, at least 0.7-fold, atleast 0.8-fold, at least 0.9-fold, at least 1.0-fold, at least 1.5-fold,at least 2.0-fold, at least 2.5-fold, at least 3.0 fold, at least3.5-fold, at least 4.0-fold, at least 4.5-fold, at least 5.0-fold, atleast 5.5-fold, at least 6.0-fold, at least 6.5-fold, at least 7.0-fold,at least 7.5-fold, at least 8.0-fold, at least 8.5-fold, at least9.0-fold, at least 9.5-fold, at least 10.0-fold, at least 10.5-fold, atleast 11.0-fold, at least 11.5-fold, at least 12.0-fold, at least12.5-fold, at least 13.0-fold, at least 13.5-fold, at least 14.0-fold,at least 14.5-fold, at least 15.0-fold, at least 15.5-fold, at least16.0-fold, at least 16.5-fold, at least 17.0-fold, at least 17.5-fold,at least 18.0-fold, at least 18.5-fold, at least 19.0-fold, at least19.5-fold, at least 20-fold greater, at least 25-fold greater, at least30-fold greater, at least 35-fold greater, at least 40-fold greater, atleast 45-fold greater, at least 50-fold greater, at least 55-foldgreater, at least 60-fold greater, at least 65-fold greater, at least70-fold greater, at least 75-fold greater, at least 80-fold greater, atleast 85-fold greater, at least 90-fold greater, at least 95-foldgreater, or at least 100-fold greater, or about 0.2-fold to about100-fold greater, about 0.2-fold to about 90-fold greater, about0.2-fold to about 80-fold greater, about 0.2-fold to about 70-foldgreater, about 0.2-fold to about 60-fold greater, about 0.2-fold toabout 50-fold greater, about 0.2-fold to about 40-fold greater, about0.2-fold to about 30-fold greater, about 0.2-fold to about 25-foldgreater, about 0.2-fold to about 20-fold greater, about 0.2-fold toabout 15-fold greater, about 0.2-fold to about 10-fold greater, about0.2-fold to about 8-fold greater, about 0.2-fold to about 5-foldgreater, about 0.2-fold to about 2-fold greater, about 0.2-fold to about1-fold greater, about 0.2-fold to about 0.5-fold greater, about 0.5-foldto about 100-fold greater, about 0.5-fold to about 90-fold greater,about 0.5-fold to about 80-fold greater, about 0.5-fold to about 70-foldgreater, about 0.5-fold to about 60-fold greater, about 0.5-fold toabout 50-fold greater, about 0.5-fold to about 40-fold greater, about0.5-fold to about 30-fold greater, about 0.5-fold to about 25-foldgreater, about 0.5-fold to about 20-fold greater, about 0.5-fold toabout 15-fold greater, about 0.5-fold to about 10-fold greater, about0.5-fold to about 8-fold greater, about 0.5-fold to about 5-foldgreater, about 0.5-fold to about 2-fold greater, about 0.5-fold to about1-fold greater, about 1-fold to about 100-fold greater, about 1-fold toabout 90-fold greater, about 1-fold to about 80-fold greater, about1-fold to about 70-fold greater, about 1-fold to about 60-fold greater,about 1-fold to about 50-fold greater, about 1-fold to about 40-foldgreater, about 1-fold to about 30-fold greater, about 1-fold to about25-fold greater, about 1-fold to about 20-fold greater, about 1-fold toabout 15-fold greater, about 1-fold to about 10-fold greater, about1-fold to about 8-fold greater, about 1-fold to about 5-fold greater,about 1-fold to about 2-fold greater, about 2-fold to about 100-foldgreater, about 2-fold to about 90-fold greater, about 2-fold to about80-fold greater, about 2-fold to about 70-fold greater, about 2-fold toabout 60-fold greater, about 2-fold to about 50-fold greater, about2-fold to about 40-fold greater, about 2-fold to about 30-fold greater,about 2-fold to about 25-fold greater, about 2-fold to about 20-foldgreater, about 2-fold to about 15-fold greater, about 2-fold to about10-fold greater, about 2-fold to about 8-fold greater, about 2-fold toabout 5-fold greater, about 5-fold to about 100-fold greater, about5-fold to about 90-fold greater, about 5-fold to about 80-fold greater,about 5-fold to about 70-fold greater, about 5-fold to about 60-foldgreater, about 5-fold to about 50-fold greater, about 5-fold to about40-fold greater, about 5-fold to about 30-fold greater, about 5-fold toabout 25-fold greater, about 5-fold to about 20-fold greater, about5-fold to about 15-fold greater, about 5-fold to about 10-fold greater,about 5-fold to about 8-fold greater, about 8-fold to about 100-foldgreater, about 8-fold to about 90-fold greater, about 8-fold to about80-fold greater, about 8-fold to about 70-fold greater, about 8-fold toabout 60-fold greater, about 8-fold to about 50-fold greater, about8-fold to about 40-fold greater, about 8-fold to about 30-fold greater,about 8-fold to about 25-fold greater, about 8-fold to about 20-foldgreater, about 8-fold to about 15-fold greater, about 8-fold to about10-fold greater, about 10-fold to about 100-fold greater, about 10-foldto about 90-fold greater, about 10-fold to about 80-fold greater, about10-fold to about 70-fold greater, about 10-fold to about 60-foldgreater, about 10-fold to about 50-fold greater, about 10-fold to about40-fold greater, about 10-fold to about 30-fold greater, about 10-foldto about 25-fold greater, about 10-fold to about 20-fold greater, about10-fold to about 15-fold greater, about 15-fold to about 100-foldgreater, about 15-fold to about 90-fold greater, about 15-fold to about80-fold greater, about 15-fold to about 70-fold greater, about 15-foldto about 60-fold greater, about 15-fold to about 50-fold greater, about15-fold to about 40-fold greater, about 15-fold to about 30-foldgreater, about 15-fold to about 25-fold greater, about 15-fold to about20-fold greater, about 20-fold to about 100-fold greater, about 20-foldto about 90-fold greater, about 20-fold to about 80-fold greater, about20-fold to about 70-fold greater, about 20-fold to about 60-foldgreater, about 20-fold to about 50-fold greater, about 20-fold to about40-fold greater, about 20-fold to about 30-fold greater, about 20-foldto about 25-fold greater, about 25-fold to about 100-fold greater, about25-fold to about 90-fold greater, about 25-fold to about 80-foldgreater, about 25-fold to about 70-fold greater, about 25-fold to about60-fold greater, about 25-fold to about 50-fold greater, about 25-foldto about 40-fold greater, about 25-fold to about 30-fold greater, about30-fold to about 100-fold greater, about 30-fold to about 90-foldgreater, about 30-fold to about 80-fold greater, about 30-fold to about70-fold greater, about 30-fold to about 60-fold greater, about 30-foldto about 50-fold greater, about 30-fold to about 40-fold greater, about40-fold to about 100-fold greater, about 40-fold to about 90-foldgreater, about 40-fold to about 80-fold greater, about 40-fold to about70-fold greater, about 40-fold to about 60-fold greater, about 40-foldto about 50-fold greater, about 50-fold to about 100-fold greater, about50-fold to about 90-fold greater, about 50-fold to about 80-foldgreater, about 50-fold to about 70-fold greater, about 50-fold to about60-fold greater, about 60-fold to about 100-fold greater, about 60-foldto about 90-fold greater, about 60-fold to about 80-fold greater, about60-fold to about 70-fold greater, about 70-fold to about 100-foldgreater, about 70-fold to about 90-fold greater, about 70-fold to about80-fold greater, about 80-fold to about 100-fold greater, about 80-foldto about 90-fold greater, or about 90-fold to about 100-fold greater),than the K_(D) at a pH of about 7.0 to about 8.0 (e.g., any of thesubranges of this range described herein).

In some embodiments of the ABPCs that include a first antigen-bindingdomain and a second antigen-binding domain, the first and secondantigen-binding domains are identical or are at least 80% identical(e.g., at least 82%, at least 84%, at least 86%, at least 88%, at least90%, at least 91%, at least 92%, at least 93%, at least 94%, at least95%, at least 96%, at least 97%, at least 98%, or at least 99%identical) in amino acid sequence to each other. In some embodiments,the ABPCs that include a first antigen-binding domain and a secondantigen-binding domain, the first antigen-binding domain and the secondantigen-binding domain have a sequence that is less than 80% identical(e.g., less than 75% identical, less than 70% identical, less than 65%identical, less than 60% identical, less than 55% identical, less than50% identical, less than 45% identical, less than 40% identical, lessthan 35% identical, less than 30% identical, less than 25% identical,less than 20% identical, less than 15% identical, less than 10%identical, or less than 5% identical) to each other. In some embodimentsof ABPCs that include a first and a second antigen-binding domain, thefirst and second antigen-binding domain binds two different epitopes(e.g., two different epitopes on FOLR1 or the first antigen-bindingdomain binding specifically to FOLR1 and the second antigen-bindingdomain binding to an antigen other than FOLR1).

In some embodiments of any of the ABPCs described herein, the K_(D) ofthe first antigen-binding domain (and optionally, the secondantigen-binding domain if present) at a pH of about 7.0 to about 8.0(e.g., any of the subranges of this range described herein) is betweenabout 1 pM to about 5 μM (e.g., about 1 pM to about 2 μM, about 1 pM toabout 1 μM, about 1 pM to about 500 nM, about 1 pM to about 250 nM,about 1 pM to about 240 nM, about 1 pM to about 230 nM, about 1 pM toabout 220 nM, about 1 pM to about 210 nM, about 1 pM to about 200 nM,about 1 pM to about 190 nM, about 1 pM to about 180 nM, about 1 pM toabout 170 nM, about 1 pM to about 160 nM, about 1 pM to about 150 nM,about 1 pM to about 140 nM, about 1 pM to about 130 nM, about 1 pM toabout 120 nM, about 1 pM to about 110 nM, about 1 pM to about 100 nM,about 1 pM to about 95 nM, about 1 pM to about 90 nM, about 1 pM toabout 85 nM, about 1 pM to about 80 nM, about 1 pM to about 75 nM, about1 pM to about 70 nM, about 1 pM to about 65 nM, about 1 pM to about 60nM, about 1 pM to about 55 nM, about 1 pM to about 50 nM, about 1 pM toabout 45 nM, about 1 pM to about 40 nM, about 1 pM to about 35 nM, about1 pM to about 30 nM, about 1 pM to about 25 nM, about 1 pM to about 20nM, about 1 pM to about 15 nM, about 1 pM to about 10 nM, about 1 pM toabout 5 nM, about 1 pM to about 2 nM, about 1 pM to about 1 nM, about 1pM to about 950 pM, about 1 pM to about 900 pM, about 1 pM to about 850pM, about 1 pM to about 800 pM, about 1 pM to about 750 pM, about 1 pMto about 700 pM, about 1 pM to about 650 pM, about 1 pM to about 600 pM,about 1 pM to about 550 pM, about 1 pM to about 500 pM, about 1 pM toabout 450 pM, about 1 pM to about 400 pM, about 1 pM to about 350 pM,about 1 pM to about 300 pM, about 1 pM to about 250 pM, about 1 pM toabout 200 pM, about 1 pM to about 150 pM, about 1 pM to about 100 pM,about 1 pM to about 90 pM, about 1 pM to about 80 pM, about 1 pM toabout 70 pM, about 1 pM to about 60 pM, about 1 pM to about 50 pM, about1 pM to about 40 pM, about 1 pM to about 30 pM, about 1 pM to about 20pM, about 1 pM to about 10 pM, about 1 pM to about 5 pM, about 1 pM toabout 4 pM, about 1 pM to about 3 pM, about 1 pM to about 2 pM, about 2pM to about 5 μM, about 2 pM to about 2 μM, about 2 pM to about 1 μM,about 2 pM to about500 nM, about 2 pM to about 250 nM, about 2 pM toabout 240 nM, about 2 pM to about 230 nM, about 2 pM to about 220 nM,about 2 pM to about 210 nM, about 2 pM to about 200 nM, about 2 pM toabout 190 nM, about 2 pM to about 180 nM, about 2 pM to about 170 nM,about 2 pM to about 160 nM, about 2 pM to about 150 nM, about 2 pM toabout 140 nM, about 2 pM to about 130 nM, about 2 pM to about 120 nM,about 2 pM to about 110 nM, about 2 pM to about 100 nM, about 2 pM toabout 95 nM, about 2 pM to about 90 nM, about 2 pM to about 85 nM, about2 pM to about 80 nM, about 2 pM to about 75 nM, about 2 pM to about 70nM, about 2 pM to about 65 nM, about 2 pM to about 60 nM, about 2 pM toabout 55 nM, about 2 pM to about 50 nM, about 2 pM to about 45 nM, about2 pM to about 40 nM, about 2 pM to about 35 nM, about 2 pM to about 30nM, about 2 pM to about 25 nM, about 2 pM to about 20 nM, about 2 pM toabout 15 nM, about 2 pM to about 10 nM, about 2 pM to about 5 nM, about2 pM to about 2 nM, about 2 pM to about 1 nM, about 2 pM to about 950pM, about 2 pM to about 900 pM, about 2 pM to about 850 pM, about 2 pMto about 800 pM, about 2 pM to about 750 pM, about 2 pM to about 700 pM,about 2 pM to about 650 pM, about 2 pM to about 600 pM, about 2 pM toabout 550 pM, about 2 pM to about 500 pM, about 2 pM to about 450 pM,about 2 pM to about 400 pM, about 2 pM to about 350 pM, about 2 pM toabout 300 pM, about 2 pM to about 250 pM, about 2 pM to about 200 pM,about 2 pM to about 150 pM, about 2 pM to about 100 pM, about 2 pM toabout 90 pM, about 2 pM to about 80 pM, about 2 pM to about 70 pM, about2 pM to about 60 pM, about 2 pM to about 50 pM, about 2 pM to about 40pM, about 2 pM to about 30 pM, about 2 pM to about 20 pM, about 2 pM toabout 10 pM, about 2 pM to about 5 pM, about 2 pM to about 4 pM, about 2pM to about 3 pM, about 5 pM to about 5 μM, about 5 pM to about 2 μM,about 5 pM to about 1 μM, about 5 pM to about 500 nM, about 5 pM toabout 250 nM, about 5 pM to about 240 nM, about 5 pM to about 230 nM,about 5 pM to about 220 nM, about 5 pM to about 210 nM, about 5 pM toabout 200 nM, about 5 pM to about 190 nM, about 5 pM to about 180 nM,about 5 pM to about 170 nM, about 5 pM to about 160 nM, about 5 pM toabout 150 nM, about 5 pM to about 140 nM, about 5 pM to about 130 nM,about 5 pM to about 120 nM, about 5 pM to about 110 nM, about 5 pM toabout 100 nM, about 5 pM to about 95 nM, about 5 pM to about 90 nM,about 5 pM to about 85 nM, about 5 pM to about 80 nM, about 5 pM toabout 75 nM, about 5 pM to about 70 nM, about 5 pM to about 65 nM, about5 pM to about 60 nM, about 5 pM to about 55 nM, about 5 pM to about 50nM, about 5 pM to about 45 nM, about 5 pM to about 40 nM, about 5 pM toabout 35 nM, about 5 pM to about 30 nM, about 5 pM to about 25 nM, about5 pM to about 20 nM, about 5 pM to about 15 nM, about 5 pM to about 10nM, about 5 pM to about 5 nM, about 5 pM to about 2 nM, about 5 pM toabout 1 nM, about 5 pM to about 950 pM, about 5 pM to about 900 pM,about 5 pM to about 850 pM, about 5 pM to about 800 pM, about 5 pM toabout 750 pM, about 5 pM to about 700 pM, about 5 pM to about 650 pM,about 5 pM to about 600 pM, about 5 pM to about 550 pM, about 5 pM toabout 500 pM, about 5 pM to about 450 pM, about 5 pM to about 400 pM,about 5 pM to about 350 pM, about 5 pM to about 300 pM, about 5 pM toabout 250 pM, about 5 pM to about 200 pM, about 5 pM to about 150 pM,about 5 pM to about 100 pM, about 5 pM to about 90 pM, about 5 pM toabout 80 pM, about 5 pM to about 70 pM, about 5 pM to about 60 pM, about5 pM to about 50 pM, about 5 pM to about 40 pM, about 5 pM to about 30pM, about 5 pM to about 20 pM, about 5 pM to about 10 pM, about 10 pM toabout 5 μM, about 10 pM to about 2 μM, about 10 pM to about 1 μM, about10 pM to about 500 nM, about 10 pM to about 250 nM, about 10 pM to about240 nM, about 10 pM to about 230 nM, about 10 pM to about 220 nM, about10 pM to about 210 nM, about 10 pM to about 200 nM, about 10 pM to about190 nM, about 10 pM to about 180 nM, about 10 pM to about 170 nM, about10 pM to about 160 nM, about 10 pM to about 150 nM, about 10 pM to about140 nM, about 10 pM to about 130 nM, about 10 pM to about 120 nM, about10 pM to about 110 nM, about 10 pM to about 100 nM, about 10 pM to about95 nM, about 10 pM to about 90 nM, about 10 pM to about 85 nM, about 10pM to about 80 nM, about 10 pM to about 75 nM, about 10 pM to about 70nM, about 10 pM to about 65 nM, about 10 pM to about 60 nM, about 10 pMto about 55 nM, about 10 pM to about 50 nM, about 10 pM to about 45 nM,about 10 pM to about 40 nM, about 10 pM to about 35 nM, about 10 pM toabout 30 nM, about 10 pM to about 25 nM, about 10 pM to about 20 nM,about 10 pM to about 15 nM, about 10 pM to about 10 nM, about 10 pM toabout 5 nM, about 10 pM to about 2 nM, about 10 pM to about 1 nM, about10 pM to about 950 pM, about 10 pM to about 900 pM, about 10 pM to about850 pM, about 10 pM to about 800 pM, about 10 pM to about 750 pM, about10 pM to about 700 pM, about 10 pM to about 650 pM, about 10 pM to about600 pM, about 10 pM to about 550 pM, about 10 pM to about 500 pM, about10 pM to about 450 pM, about 10 pM to about 400 pM, about 10 pM to about350 pM, about 10 pM to about 300 pM, about 10 pM to about 250 pM, about10 pM to about 200 pM, about 10 pM to about 150 pM, about 10 pM to about100 pM, about 10 pM to about 90 pM, about 10 pM to about 80 pM, about 10pM to about 70 pM, about 10 pM to about 60 pM, about 10 pM to about 50pM, about 10 pM to about 40 pM, about 10 pM to about 30 pM, about 10 pMto about 20 pM, about 15 pM to about 5 μM, about 15 pM to about 2 μM,about 15 pM to about 1 μM, about 15 pM to about 500 nM, about 15 pM toabout 250 nM, about 15 pM to about 240 nM, about 15 pM to about 230 nM,about 15 pM to about 220 nM, about 15 pM to about 210 nM, about 15 pM toabout 200 nM, about 15 pM to about 190 nM, about 15 pM to about 180 nM,about 15 pM to about 170 nM, about 15 pM to about 160 nM, about 15 pM toabout 150 nM, about 15 pM to about 140 nM, about 15 pM to about 130 nM,about 15 pM to about 120 nM, about 15 pM to about 110 nM, about 15 pM toabout 100 nM, about 15 pM to about 95 nM, about 15 pM to about 90 nM,about 15 pM to about 85 nM, about 15 pM to about 80 nM, about 15 pM toabout 75 nM, about 15 pM to about 70 nM, about 15 pM to about 65 nM,about 15 pM to about 60 nM, about 15 pM to about 55 nM, about 15 pM toabout 50 nM, about 15 pM to about 45 nM, about 15 pM to about 40 nM,about 15 pM to about 35 nM, about 15 pM to about 30 nM, about 15 pM toabout 25 nM, about 15 pM to about 20 nM, about 15 pM to about 15 nM,about 15 pM to about 10 nM, about 15 pM to about 5 nM, about 15 pM toabout 2 nM, about 15 pM to about 1 nM, about 15 pM to about 950 pM,about 15 pM to about 900 pM, about 15 pM to about 850 pM, about 15 pM toabout 800 pM, about 15 pM to about 750 pM, about 15 pM to about 700 pM,about 15 pM to about 650 pM, about 15 pM to about 600 pM, about 15 pM toabout 550 pM, about 15 pM to about 500 pM, about 15 pM to about 450 pM,about 15 pM to about 400 pM, about 15 pM to about 350 pM, about 15 pM toabout 300 pM, about 15 pM to about 250 pM, about 15 pM to about 200 pM,about 15 pM to about 150 pM, about 15 pM to about 100 pM, about 15 pM toabout 90 pM, about 15 pM to about 80 pM, about 15 pM to about 70 pM,about 15 pM to about 60 pM, about 15 pM to about 50 pM, about 15 pM toabout 40 pM, about 15 pM to about 30 pM, about 15 pM to about 20 pM,about 20 pM to about 5 μM, about 20 pM to about 2 μM, about 20 pM toabout 1 μM, about 20 pM to about 500 nM, about 20 pM to about 250 nM,about 20 pM to about 240 nM, about 20 pM to about 230 nM, about 20 pM toabout 220 nM, about 20 pM to about 210 nM, about 20 pM to about 200 nM,about 20 pM to about 190 nM, about 20 pM to about 180 nM, about 20 pM toabout 170 nM, about 20 pM to about 160 nM, about 20 pM to about 150 nM,about 20 pM to about 140 nM, about 20 pM to about 130 nM, about 20 pM toabout 120 nM, about 20 pM to about 110 nM, about 20 pM to about 100 nM,about 20 pM to about 95 nM, about 20 pM to about 90 nM, about 20 pM toabout 85 nM, about 20 pM to about 80 nM, about 20 pM to about 75 nM,about 20 pM to about 70 nM, about 20 pM to about 65 nM, about 20 pM toabout 60 nM, about 20 pM to about 55 nM, about 20 pM to about 50 nM,about 20 pM to about 45 nM, about 20 pM to about 40 nM, about 20 pM toabout 35 nM, about 20 pM to about 30 nM, about 20 pM to about 25 nM,about 20 pM to about 20 nM, about 20 pM to about 15 nM, about 20 pM toabout 10 nM, about 20 pM to about 5 nM, about 20 pM to about 2 nM, about20 pM to about 1 nM, about 20 pM to about 950 pM, about 20 pM to about900 pM, about 20 pM to about 850 pM, about 20 pM to about 800 pM, about20 pM to about 750 pM, about 20 pM to about 700 pM, about 20 pM to about650 pM, about 20 pM to about 600 pM, about 20 pM to about 550 pM, about20 pM to about 500 pM, about 20 pM to about 450 pM, about 20 pM to about400 pM, about 20 pM to about 350 pM, about 20 pM to about 300 pM, about20 pM to about 250 pM, about 20 pM to about 20 pM, about 200 pM to about150 pM, about 20 pM to about 100 pM, about 20 pM to about 90 pM, about20 pM to about 80 pM, about 20 pM to about 70 pM, about 20 pM to about60 pM, about 20 pM to about 50 pM, about 20 pM to about 40 pM, about 20pM to about 30 pM, about 30 pM to about 5 μM, about 30 pM to about 2 μM,about 30 pM to about 1 μM, about 30 pM to about 500 nM, about 30 pM toabout 250 nM, about 30 pM to about 240 nM, about 30 pM to about 230 nM,about 30 pM to about 220 nM, about 30 pM to about 210 nM, about 30 pM toabout 200 nM, about 30 pM to about 190 nM, about 30 pM to about 180 nM,about 30 pM to about 170 nM, about 30 pM to about 160 nM, about 30 pM toabout 150 nM, about 30 pM to about 140 nM, about 30 pM to about 130 nM,about 30 pM to about 120 nM, about 30 pM to about 110 nM, about 30 pM toabout 100 nM, about 30 pM to about 95 nM, about 30 pM to about 90 nM,about 30 pM to about 85 nM, about 30 pM to about 80 nM, about 30 pM toabout 75 nM, about 30 pM to about 70 nM, about 30 pM to about 65 nM,about 30 pM to about 60 nM, about 30 pM to about 55 nM, about 30 pM toabout 50 nM, about 30 pM to about 45 nM, about 30 pM to about 40 nM,about 30 pM to about 35 nM, about 30 pM to about 30 nM, about 30 pM toabout 25 nM, about 30 pM to about 20 nM, about 30 pM to about 15 nM,about 30 pM to about 10 nM, about 30 pM to about 5 nM, about 30 pM toabout 2 nM, about 30 pM to about 1 nM, about 30 pM to about 950 pM,about 30 pM to about 900 pM, about 30 pM to about 850 pM, about 30 pM toabout 800 pM, about 30 pM to about 750 pM, about 30 pM to about 700 pM,about 30 pM to about 650 pM, about 30 pM to about 600 pM, about 30 pM toabout 550 pM, about 30 pM to about 500 pM, about 30 pM to about 450 pM,about 30 pM to about 400 pM, about 30 pM to about 350 pM, about 30 pM toabout 300 pM, about 30 pM to about 250 pM, about 30 pM to about 200 pM,about 30 pM to about 150 pM, about 30 pM to about 100 pM, about 30 pM toabout 90 pM, about 30 pM to about 80 pM, about 30 pM to about 70 pM,about 30 pM to about 60 pM, about 30 pM to about 50 pM, about 30 pM toabout 40 pM, about 40 pM to about 5 μM, about 40 pM to about 2 μM, about40 pM to about 1 μM, about 40 pM to about 500 nM, about 40 pM to about250 nM, about 40 pM to about 240 nM, about 40 pM to about 230 nM, about40 pM to about 220 nM, about 40 pM to about 210 nM, about 40 pM to about200 nM, about 40 pM to about 190 nM, about 40 pM to about 180 nM, about40 pM to about 170 nM, about 40 pM to about 160 nM, about 40 pM to about150 nM, about 40 pM to about 140 nM, about 40 pM to about 130 nM, about40 pM to about 120 nM, about 40 pM to about 110 nM, about 40 pM to about100 nM, about 40 pM to about 95 nM, about 40 pM to about 90 nM, about 40pM to about 85 nM, about 40 pM to about 80 nM, about 40 pM to about 75nM, about 40 pM to about 70 nM, about 40 pM to about 65 nM, about 40 pMto about 60 nM, about 40 pM to about 55 nM, about 40 pM to about 50 nM,about 40 pM to about 45 nM, about 40 pM to about 40 nM, about 40 pM toabout 35 nM, about 40 pM to about 30 nM, about 40 pM to about 25 nM,about 40 pM to about 30 nM, about 40 pM to about 15 nM, about 40 pM toabout 10 nM, about 40 pM to about 5 nM, about 40 pM to about 2 nM, about40 pM to about 1 nM, about 40 pM to about 950 pM, about 40 pM to about900 pM, about 40 pM to about 850 pM, about 40 pM to about 800 pM, about40 pM to about 750 pM, about 40 pM to about 700 pM, about 40 pM to about650 pM, about 40 pM to about 600 pM, about 40 pM to about 550 pM, about40 pM to about 500 pM, about 40 pM to about 450 pM, about 40 pM to about400 pM, about 40 pM to about 350 pM, about 40 pM to about 300 pM, about40 pM to about 250 pM, about 40 pM to about 200 pM, about 40 pM to about150 pM, about 40 pM to about 100 pM, about 40 pM to about 90 pM, about40 pM to about 80 pM, about 40 pM to about 70 pM, about 40 pM to about60 pM, about 40 pM to about 50 pM, about 50 pM to about 5 μM, about 50pM to about 2 μM, about 50 pM to about 1 μM, about 50 pM to about 500nM, about 50 pM to about 250 nM, about 50 pM to about 240 nM, about 50pM to about 230 nM, about 50 pM to about 220 nM, about 50 pM to about210 nM, about 50 pM to about 200 nM, about 50 pM to about 190 nM, about50 pM to about 180 nM; about 50 pM to about 170 nM, about 50 pM to about160 nM, about 50 pM to about 150 nM, about 50 pM to about 140 nM, about50 pM to about 130 nM, about 50 pM to about 120 nM, about 50 pM to about110 nM, about 50 pM to about 100 nM, about 50 pM to about 95 nM, about50 pM to about 90 nM, about 50 pM to about 85 nM, about 50 pM to about80 nM, about 50 pM to about 75 nM, about 50 pM to about 70 nM, about 50pM to about 65 nM, about 50 pM to about 60 nM, about 50 pM to about 55nM, about 50 pM to about 50 nM, about 50 pM to about 45 nM, about 50 pMto about 40 nM, about 50 pM to about 35 nM, about 50 pM to about 30 nM,about 50 pM to about 25 nM, about 50 pM to about 30 nM, about 50 pM toabout 15 nM, about 50 pM to about 10 nM, about 50 pM to about 5 nM,about 50 pM to about 2 nM, about 50 pM to about 1 nM, about 50 pM toabout 950 pM, about 50 pM to about 900 pM, about 50 pM to about 850 pM,about 50 pM to about 800 pM, about 50 pM to about 750 pM, about 50 pM toabout 700 pM, about 50 pM to about 650 pM, about 50 pM to about 600 pM,about 50 pM to about 550 pM, about 50 pM to about 500 pM, about 50 pM toabout 450 pM, about 50 pM to about 400 pM, about 50 pM to about 350 pM,about 50 pM to about 300 pM, about 50 pM to about 250 pM, about 50 pM toabout 200 pM, about 50 pM to about 150 pM, about 50 pM to about 100 pM,about 50 pM to about 90 pM, about 50 pM to about 80 pM, about 50 pM toabout 70 pM, about 50 pM to about 60 pM, about 60 pM to about 5 μM,about 60 pM to about 2 μM, about 60 pM to about 1 μM, about 60 pM toabout 500 nM, about 60 pM to about 250 nM, about 60 pM to about 240 nM,about 60 pM to about 230 nM, about 60 pM to about 220 nM, about 60 pM toabout 210 nM, about 60 pM to about 200 nM, about 60 pM to about 190 nM,about 60 pM to about 180 nM, about 60 pM to about 170 nM, about 60 pM toabout 160 nM, about 60 pM to about 150 nM, about 60 pM to about 140 nM,about 60 pM to about 130 nM, about 60 pM to about 120 nM, about 60 pM toabout 110 nM, about 60 pM to about 100 nM, about 60 pM to about 95 nM,about 60 pM to about 90 nM, about 60 pM to about 85 nM, about 60 pM toabout 80 nM, about 60 pM to about 75 nM, about 60 pM to about 70 nM,about 60 pM to about 65 nM, about 60 pM to about 60 nM, about 60 pM toabout 55 nM, about 60 pM to about 50 nM, about 60 pM to about 45 nM,about 60 pM to about 40 nM, about 60 pM to about 35 nM, about 60 pM toabout 30 nM, about 60 pM to about 25 nM, about 60 pM to about 20 nM,about 60 pM to about 15 nM, about 60 pM to about 10 nM, about 60 pM toabout 5 nM, about 60 pM to about 2 nM, about 60 pM to about 1 nM, about60 pM to about 950 pM, about 60 pM to about 900 pM, about 60 pM to about850 pM, about 60 pM to about 800 pM, about 60 pM to about 750 pM, about60 pM to about 700 pM, about 60 pM to about 650 pM, about 60 pM to about600 pM, about 60 pM to about 550 pM, about 60 pM to about 500 pM, about60 pM to about 450 pM, about 60 pM to about 400 pM, about 60 pM to about350 pM, about 60 pM to about 300 pM, about 60 pM to about 250 pM, about60 pM to about 200 pM, about 60 pM to about 150 pM, about 60 pM to about100 pM, about 60 pM to about 90 pM, about 60 pM to about 80 pM, about 60pM to about 70 pM, about 70 pM to about 5 μM, about 70 pM to about 2 μM,about 70 pM to about 1 μM, about 70 pM to about 500 nM, about 70 pM toabout 250 nM, about 70 pM to about 240 nM, about 70 pM to about 230 nM,about 70 pM to about 220 nM, about 70 pM to about 210 nM, about 70 pM toabout 200 nM, about 70 pM to about 190 nM, about 70 pM to about 180 nM,about 70 pM to about 170 nM, about 70 pM to about 160 nM, about 70 pM toabout 150 nM, about 70 pM to about 140 nM, about 70 pM to about 130 nM,about 70 pM to about 120 nM, about 70 pM to about 110 nM, about 70 pM toabout 100 nM, about 70 pM to about 95 nM, about 70 pM to about 90 nM,about 70 pM to about 85 nM, about 70 pM to about 80 nM, about 70 pM toabout 75 nM, about 70 pM to about 70 nM, about 70 pM to about 65 nM,about 70 pM to about 60 nM, about 70 pM to about 55 nM, about 70 pM toabout 50 nM, about 70 pM to about 45 nM, about 70 pM to about 40 nM,about 70 pM to about 35 nM, about 70 pM to about 30 nM, about 70 pM toabout 25 nM, about 70 pM to about 20 nM, about 70 pM to about 15 nM,about 70 pM to about 10 nM, about 70 pM to about 5 nM, about 70 pM toabout 2 nM, about 70 pM to about 1 nM, about 70 pM to about 950 pM,about 70 pM to about 900 pM, about 70 pM to about 850 pM, about 70 pM toabout 800 pM, about 70 pM to about 750 pM, about 70 pM to about 700 pM,about 70 pM to about 650 pM, about 70 pM to about 600 pM, about 70 pM toabout 550 pM, about 70 pM to about 500 pM, about 70 pM to about 450 pM,about 70 pM to about 400 pM, about 70 pM to about 350 pM, about 70 pM toabout 300 pM, about 70 pM to about 250 pM, about 70 pM to about 200 pM,about 70 pM to about 150 pM, about 70 pM to about 100 pM, about 70 pM toabout 90 pM, about 70 pM to about 80 pM, about 80 pM to about 5 μM,about 80 pM to about 2 μM, about 80 pM to about 1 μM, about 80 pM toabout 500 nM, about 80 pM to about 250 nM, about 80 pM to about 240 nM,about 80 pM to about 230 nM, about 80 pM to about 220 nM, about 80 pM toabout 210 nM, about 80 pM to about 200 nM, about 80 pM to about 190 nM,about 80 pM to about 180 nM, about 80 pM to about 170 nM, about 80 pM toabout 160 nM, about 80 pM to about 150 nM, about 80 pM to about 140 nM,about 80 pM to about 130 nM, about 80 pM to about 120 nM, about 80 pM toabout 110 nM, about 80 pM to about 100 nM, about 80 pM to about 95 nM,about 80 pM to about 90 nM, about 80 pM to about 85 nM, about 80 pM toabout 80 nM, about 80 pM to about 75 nM, about 80 pM to about 70 nM,about 80 pM to about 65 nM, about 80 pM to about 60 nM, about 80 pM toabout 55 nM, about 80 pM to about 50 nM, about 80 pM to about 45 nM,about 80 pM to about 40 nM, about 80 pM to about 35 nM, about 80 pM toabout 30 nM, about 80 pM to about 25 nM, about 80 pM to about 20 nM,about 80 pM to about 15 nM, about 80 pM to about 10 nM, about 80 pM toabout 5 nM, about 80 pM to about 2 nM, about 80 pM to about 1 nM, about80 pM to about 950 pM, about 80 pM to about 900 pM, about 80 pM to about850 pM, about 80 pM to about 800 pM, about 80 pM to about 750 pM, about80 pM to about 700 pM, about 80 pM to about 650 pM, about 80 pM to about600 pM, about 80 pM to about 550 pM, about 80 pM to about 500 pM, about80 pM to about 450 pM, about 80 pM to about 400 pM, about 80 pM to about350 pM, about 80 pM to about 300 pM, about 80 pM to about 250 pM, about80 pM to about 200 pM, about 80 pM to about 150 pM, about 80 pM to about100 pM, about 80 pM to about 90 pM, about 90 pM to about 5 μM, about 90pM to about 2 μM, about 90 pM to about 1 μM, about 90 pM to about 500nM, about 90 pM to about 250 nM, about 90 pM to about 240 nM, about 90pM to about 230 nM, about 90 pM to about 220 nM, about 90 pM to about210 nM, about 90 pM to about 200 nM, about 90 pM to about 190 nM, about90 pM to about 180 nM, about 90 pM to about 170 nM, about 90 pM to about160 nM, about 90 pM to about 150 nM, about 90 pM to about 140 nM, about90 pM to about 130 nM, about 90 pM to about 120 nM, about 90 pM to about110 nM, about 90 pM to about 100 nM, about 90 pM to about 95 nM, about90 pM to about 90 nM, about 90 pM to about 85 nM, about 90 pM to about80 nM, about 90 pM to about 75 nM, about 90 pM to about 70 nM, about 90pM to about 65 nM, about 90 pM to about 60 nM, about 90 pM to about 55nM, about 90 pM to about 50 nM, about 90 pM to about 45 nM, about 90 pMto about 40 nM, about 90 pM to about 35 nM, about 90 pM to about 30 nM,about 90 pM to about 25 nM, about 90 pM to about 30 nM, about 90 pM toabout 15 nM, about 90 pM to about 10 nM, about 90 pM to about 5 nM,about 90 pM to about 2 nM, about 90 pM to about 1 nM, about 90 pM toabout 950 pM, about 90 pM to about 900 pM, about 90 pM to about 850 pM,about 90 pM to about 800 pM, about 90 pM to about 750 pM, about 90 pM toabout 700 pM, about 90 pM to about 650 pM, about 90 pM to about 600 pM,about 90 pM to about 550 pM, about 90 pM to about 500 pM, about 90 pM toabout 450 pM, about 90 pM to about 400 pM, about 90 pM to about 350 pM,about 90 pM to about 300 pM, about 90 pM to about 250 pM, about 90 pM toabout 200 pM, about 90 pM to about 150 pM, about 90 pM to about 100 pM,about 100 pM to about 30 nM, about 100 pM to about 25 nM, about 100 pMto about 5 μM, about 100 pM to about 2 μM, about 100 pM to about 1 μM,about 100 pM to about 500 nM, about 100 pM to about 250 nM, about 100 pMto about 240 nM, about 100 pM to about 230 nM, about 100 pM to about 220nM, about 100 pM to about 210 nM, about 100 pM to about 200 nM, about100 pM to about 190 nM, about 100 pM to about 180 nM, about 100 pM toabout 170 nM, about 100 pM to about 160 nM, about 100 pM to about 150nM, about 100 pM to about 140 nM, about 100 pM to about 130 nM, about100 pM to about 120 nM, about 100 pM to about 110 nM, about 100 pM toabout 100 nM, about 100 pM to about 95 nM, about 100 pM to about 90 nM,about 100 pM to about 85 nM, about 100 pM to about 80 nM, about 100 pMto about 75 nM, about 100 pM to about 70 nM, about 100 pM to about 65nM, about 100 pM to about 60 nM, about 100 pM to about 55 nM, about 100pM to about 50 nM, about 100 pM to about 45 nM, about 100 pM to about 40nM, about 100 pM to about 35 nM, about 100 pM to about 30 nM, about 100pM to about 15 nM, about 100 pM to about 10 nM, about 100 pM to about 5nM, about 100 pM to about 2 nM, about 100 pM to about 1 nM, about 100 pMto about 950 pM, about 100 pM to about 900 pM, about 100 pM to about 850pM, about 100 pM to about 800 pM, about 100 pM to about 750 pM, about100 pM to about 700 pM, about 100 pM to about 650 pM, about 100 pM toabout 600 pM, about 100 pM to about 550 pM, about 100 pM to about 500pM, about 100 pM to about 450 pM, about 100 pM to about 400 pM, about100 pM to about 350 pM, about 100 pM to about 300 pM, about 100 pM toabout 250 pM, about 100 pM to about 200 pM, about 100 pM to about 150pM, about 150 pM to about 5 μM, about 150 pM to about 2 μM, about 150 pMto about 1 μM, about 150 pM to about 500 nM, about 150 pM to about 250nM, about 150 pM to about 240 nM, about 150 pM to about 230 nM, about150 pM to about 220 nM, about 150 pM to about 210 nM, about 150 pM toabout 200 nM, about 150 pM to about 190 nM, about 150 pM to about 180nM, about 150 pM to about 170 nM, about 150 pM to about 160 nM, about150 pM to about 150 nM, about 150 pM to about 140 nM, about 150 pM toabout 130 nM, about 150 pM to about 120 nM, about 150 pM to about 110nM, about 150 pM to about 100 nM, about 150 pM to about 95 nM, about 150pM to about 90 nM, about 150 pM to about 85 nM, about 150 pM to about 80nM, about 150 pM to about 75 nM, about 150 pM to about 70 nM, about 150pM to about 65 nM, about 150 pM to about 60 nM, about 150 pM to about 55nM, about 150 pM to about 50 nM, about 150 pM to about 45 nM, about 150pM to about 40 nM, about 150 pM to about 35 nM, about 150 pM to about 30nM, about 150 pM to about 25 nM, about 150 pM to about 30 nM, about 150pM to about 15 nM, about 150 pM to about 10 nM, about 150 pM to about 5nM, about 150 pM to about 2 nM, about 150 pM to about 1 nM, about 150 pMto about 950 pM, about 150 pM to about 900 pM, about 150 pM to about 850pM, about 150 pM to about 800 pM, about 150 pM to about 750 pM, about150 pM to about 700 pM, about 150 pM to about 650 pM, about 150 pM toabout 600 pM, about 150 pM to about 550 pM, about 150 pM to about 500pM, about 150 pM to about 450 pM, about 150 pM to about 400 pM, about150 pM to about 350 pM, about 150 pM to about 300 pM, about 150 pM toabout 250 pM, about 150 pM to about 200 pM, about 200 pM to about 5 μM,about 200 pM to about 2 μM, about 200 pM to about 1 μM, about 200 pM toabout 500 nM, about 200 pM to about 250 nM, about 200 pM to about 240nM, about 200 pM to about 230 nM, about 200 pM to about 220 nM, about200 pM to about 210 nM, about 200 pM to about 200 nM, about 200 pM toabout 190 nM, about 200 pM to about 180 nM, about 200 pM to about 170nM, about 200 pM to about 160 nM, about 200 pM to about 150 nM, about200 pM to about 140 nM, about 200 pM to about 130 nM, about 200 pM toabout 120 nM, about 200 pM to about 110 nM, about 200 pM to about 100nM, about 200 pM to about 95 nM, about 200 pM to about 90 nM, about 200pM to about 85 nM, about 200 pM to about 80 nM, about 200 pM to about 75nM, about 200 pM to about 70 nM, about 200 pM to about 65 nM, about 200pM to about 60 nM, about 200 pM to about 55 nM, about 200 pM to about 50nM, about 200 pM to about 45 nM, about 200 pM to about 40 nM, about 200pM to about 35 nM, about 200 pM to about 30 nM, about 200 pM to about 25nM, about 200 pM to about 30 nM, about 200 pM to about 15 nM, about 200pM to about 10 nM, about 200 pM to about 5 nM, about 200 pM to about 2nM, about 200 pM to about 1 nM, about 200 pM to about 950 pM, about 200pM to about 900 pM, about 200 pM to about 850 pM, about 200 pM to about800 pM, about 200 pM to about 750 pM, about 200 pM to about 700 pM,about 200 pM to about 650 pM, about 200 pM to about 600 pM, about 200 pMto about 550 pM, about 200 pM to about 500 pM, about 200 pM to about 450pM, about 200 pM to about 400 pM, about 200 pM to about 350 pM, about200 pM to about 300 pM, about 200 pM to about 250 pM, about 300 pM toabout 30 nM, about 300 pM to about 25 nM, about 300 pM to about 5 μM,about 300 pM to about 2 μM, about 300 pM to about 1 μM, about 300 pM toabout 500 nM, about 300 pM to about 250 nM, about 300 pM to about 240nM, about 300 pM to about 230 nM, about 300 pM to about 220 nM, about300 pM to about 210 nM, about 300 pM to about 200 nM, about 300 pM toabout 190 nM, about 300 pM to about 180 nM, about 300 pM to about 170nM, about 300 pM to about 160 nM, about 300 pM to about 150 nM, about300 pM to about 140 nM, about 300 pM to about 130 nM, about 300 pM toabout 120 nM, about 300 pM to about 110 nM, about 300 pM to about 100nM, about 300 pM to about 95 nM, about 300 pM to about 90 nM, about 300pM to about 85 nM, about 300 pM to about 80 nM, about 300 pM to about 75nM, about 300 pM to about 70 nM, about 300 pM to about 65 nM, about 300pM to about 60 nM, about 300 pM to about 55 nM, about 300 pM to about 50nM, about 300 pM to about 45 nM, about 300 pM to about 40 nM, about 300pM to about 35 nM, about 300 pM to about 30 nM, about 300 pM to about 15nM, about 300 pM to about 10 nM, about 300 pM to about 5 nM, about 300pM to about 2 nM, about 300 pM to about 1 nM, about 300 pM to about 950pM, about 300 pM to about 900 pM, about 300 pM to about 850 pM, about300 pM to about 800 pM, about 300 pM to about 750 pM, about 300 pM toabout 700 pM, about 300 pM to about 650 pM, about 300 pM to about 600pM, about 300 pM to about 550 pM, about 300 pM to about 500 pM, about300 pM to about 450 pM, about 300 pM to about 400 pM, about 300 pM toabout 350 pM, about 400 pM to about 5 μM, about 400 pM to about 2 μM,about 400 pM to about 1 μM, about 400 pM to about 500 nM, about 400 pMto about 250 nM, about 400 pM to about 240 nM, about 400 pM to about 230nM, about 400 pM to about 220 nM, about 400 pM to about 210 nM, about400 pM to about 200 nM, about 400 pM to about 190 nM, about 400 pM toabout 180 nM, about 400 pM to about 170 nM, about 400 pM to about 160nM, about 400 pM to about 150 nM, about 400 pM to about 140 nM, about400 pM to about 130 nM, about 400 pM to about 120 nM, about 400 pM toabout 110 nM, about 400 pM to about 100 nM, about 400 pM to about 95 nM,about 400 pM to about 90 nM, about 400 pM to about 85 nM, about 400 pMto about 80 nM, about 400 pM to about 75 nM, about 400 pM to about 70nM, about 400 pM to about 65 nM, about 400 pM to about 60 nM, about 400pM to about 55 nM, about 400 pM to about 50 nM, about 400 pM to about 45nM, about 400 pM to about 40 nM, about 400 pM to about 35 nM, about 400pM to about 30 nM, about 400 pM to about 25 nM, about 400 pM to about 20nM, about 400 pM to about 15 nM, about 400 pM to about 10 nM, about 400pM to about 5 nM, about 400 pM to about 2 nM, about 400 pM to about 1nM, about 400 pM to about 950 pM, about 400 pM to about 900 pM, about400 pM to about 850 pM, about 400 pM to about 800 pM, about 400 pM toabout 750 pM, about 400 pM to about 700 pM, about 400 pM to about 650pM, about 400 pM to about 600 pM, about 400 pM to about 550 pM, about400 pM to about 500 pM, about 500 pM to about 5 μM, about 500 pM toabout 2 μM, about 500 pM to about 1 μM, about 500 pM to about 500 nM,about 500 pM to about 250 nM, about 500 pM to about 240 nM, about 500 pMto about 230 nM, about 500 pM to about 220 nM, about 500 pM to about 210nM, about 500 pM to about 200 nM, about 500 pM to about 190 nM, about500 pM to about 180 nM, about 500 pM to about 170 nM, about 500 pM toabout 160 nM, about 500 pM to about 150 nM, about 500 pM to about 140nM, about 500 pM to about 130 nM, about 500 pM to about 120 nM, about500 pM to about 110 nM, about 500 pM to about 100 nM, about 500 pM toabout 95 nM, about 500 pM to about 90 nM, about 500 pM to about 85 nM,about 500 pM to about 80 nM, about 500 pM to about 75 nM, about 500 pMto about 70 nM, about 500 pM to about 65 nM, about 500 pM to about 60nM, about 500 pM to about 55 nM, about 500 pM to about 50 nM, about 500pM to about 45 nM, about 500 pM to about 40 nM, about 500 pM to about 35nM, about 500 pM to about 30 nM, about 500 pM to about 25 nM, about 500pM to about 20 nM, about 500 pM to about 15 nM, about 500 pM to about 10nM, about 500 pM to about 5 nM, about 500 pM to about 2 nM, about 500 pMto about 1 nM, about 500 pM to about 950 pM, about 500 pM to about 900pM, about 500 pM to about 850 pM, about 500 pM to about 800 pM, about500 pM to about 750 pM, about 500 pM to about 700 pM, about 500 pM toabout 650 pM, about 500 pM to about 600 pM, about 500 pM to about 550pM, about 600 pM to about 5 μM, about 600 pM to about 2 μM, about 600 pMto about 1 μM, about 600 pM to about 500 nM, about 600 pM to about 250nM, about 600 pM to about 240 nM, about 600 pM to about 230 nM, about600 pM to about 220 nM, about 600 pM to about 210 nM, about 600 pM toabout 200 nM, about 600 pM to about 190 nM, about 600 pM to about 180nM, about 600 pM to about 170 nM, about 600 pM to about 160 nM, about600 pM to about 150 nM, about 600 pM to about MO nM, about 600 pM toabout 130 nM, about 600 pM to about 120 nM, about 600 pM to about 110nM, about 600 pM to about 100 nM, about 600 pM to about 95 nM, about 600pM to about 90 nM, about 600 pM to about 85 nM, about 600 pM to about 80nM, about 600 pM to about 75 nM, about 600 pM to about 70 nM, about 600pM to about 65 nM, about 600 pM to about 60 nM, about 600 pM to about 55nM, about 600 pM to about 50 nM, about 600 pM to about 45 nM, about 600pM to about 40 nM, about 600 pM to about 35 nM, about 600 pM to about 30nM, about 600 pM to about 25 nM, about 600 pM to about 20 nM, about 600pM to about 15 nM, about 600 pM to about 10 nM, about 600 pM to about 5nM, about 600 pM to about 2 nM, about 600 pM to about 1 nM, about 600 pMto about 950 pM, about 600 pM to about 900 pM, about 600 pM to about 850pM, about 600 pM to about 800 pM, about 600 pM to about 750 pM, about600 pM to about 700 pM, about 600 pM to about 650 pM, about 700 pM toabout 5 μM, about 700 pM to about 2 μM, about 700 pM to about 1 μM,about 700 pM to about 500 nM, about 700 pM to about 250 nM, about 700 pMto about 240 nM, about 700 pM to about 230 nM, about 700 pM to about 220nM, about 700 pM to about 210 nM, about 700 pM to about 200 nM, about700 pM to about 190 nM, about 700 pM to about 180 nM, about 700 pM toabout 170 nM, about 700 pM to about 160 nM, about 700 pM to about 150nM, about 700 pM to about 140 nM, about 700 pM to about 130 nM, about700 pM to about 120 nM, about 700 pM to about 110 nM, about 700 pM toabout 100 nM, about 700 pM to about 95 nM, about 700 pM to about 90 nM,about 700 pM to about 85 nM, about 700 pM to about 80 nM, about 700 pMto about 75 nM, about 700 pM to about 70 nM, about 700 pM to about 65nM, about 700 pM to about 60 nM, about 700 pM to about 55 nM, about 700pM to about 50 nM, about 700 pM to about 45 nM, about 700 pM to about 40nM, about 700 pM to about 35 nM, about 700 pM to about 30 nM, about 700pM to about 25 nM, about 700 pM to about 20 nM, about 700 pM to about 15nM, about 700 pM to about 10 nM, about 700 pM to about 5 nM, about 700pM to about 2 nM, about 700 pM to about 1 nM, about 700 pM to about 950pM, about 700 pM to about 900 pM, about 700 pM to about 850 pM, about700 pM to about 800 pM, about 700 pM to about 750 pM, about 800 pM toabout 5 μM, about 800 pM to about 2 μM, about 800 pM to about 1 μM,about 800 pM to about 500 nM, about 800 pM to about 250 nM, about 800 pMto about 240 nM, about 800 pM to about 230 nM, about 800 pM to about 220nM, about 800 pM to about 210 nM, about 800 pM to about 200 nM, about800 pM to about 190 nM, about 800 pM to about 180 nM, about 800 pM toabout 170 nM, about 800 pM to about 160 nM, about 800 pM to about 150nM, about 800 pM to about 140 nM, about 800 pM to about 130 nM, about800 pM to about 120 nM, about 800 pM to about 110 nM, about 800 pM toabout 100 nM, about 800 pM to about 95 nM, about 800 pM to about 90 nM,about 800 pM to about 85 nM, about 800 pM to about 80 nM, about 800 pMto about 75 nM, about 800 pM to about 70 nM, about 800 pM to about 65nM, about 800 pM to about 60 nM, about 800 pM to about 55 nM, about 800pM to about 50 nM, about 800 pM to about 45 nM, about 800 pM to about 40nM, about 800 pM to about 35 nM, about 800 pM to about 30 nM, about 800pM to about 25 nM, about 800 pM to about 20 nM, about 800 pM to about 15nM, about 800 pM to about 10 nM, about 800 pM to about 5 nM, about 800pM to about 2 nM, about 800 pM to about 1 nM, about 800 pM to about 950pM, about 800 pM to about 900 pM, about 800 pM to about 850 pM, about900 pM to about 5 μM, about 900 pM to about 2 μM, about 900 pM to about1 μM, about 900 pM to about 500 nM, about 900 pM to about 250 nM, about900 pM to about 240 nM, about 900 pM to about 230 nM, about 900 pM toabout 220 nM, about 900 pM to about 210 nM, about 900 pM to about 200nM, about 900 pM to about 190 nM, about 900 pM to about 180 nM, about900 pM to about 170 nM, about 900 pM to about 160 nM, about 900 pM toabout 150 nM, about 900 pM to about 140 nM, about 900 pM to about 130nM, about 900 pM to about 120 nM, about 900 pM to about 110 nM, about900 pM to about 100 nM, about 900 pM to about 95 nM, about 900 pM toabout 90 nM, about 900 pM to about 85 nM, about 900 pM to about 80 nM,about 900 pM to about 75 nM, about 900 pM to about 70 nM, about 900 pMto about 65 nM, about 900 pM to about 60 nM, about 900 pM to about 55nM, about 900 pM to about 50 nM, about 900 pM to about 45 nM, about 900pM to about 40 nM, about 900 pM to about 35 nM, about 900 pM to about 30nM, about 900 pM to about 25 nM, about 900 pM to about 20 nM, about 900pM to about 15 nM, about 900 pM to about 10 nM, about 900 pM to about 5nM, about 900 pM to about 2 nM, about 900 pM to about 1 nM, about 900 pMto about 950 pM, about 1 nM to about 5 μM, about 1 nM to about 2 μM,about 1 nM to about 1 μM, about 1 nM to about 500 nM, about 1 nM toabout 250 nM, about 1 nM to about 240 nM, about 1 nM to about 230 nM,about 1 nM to about 220 nM, about 1 nM to about 210 nM, about 1 nM toabout 200 nM, about 1 nM to about 190 nM, about 1 nM to about 180 nM,about 1 nM to about 170 nM, about 1 nM to about 160 nM, about 1 nM toabout 150 nM, about 1 nM to about 140 nM, about 1 nM to about 130 nM,about 1 nM to about 120 nM, about 1 nM to about 110 nM, about 1 nM toabout 100 nM, about 1 nM to about 95 nM, about 1 nM to about 90 nM,about 1 nM to about 85 nM, about 1 nM to about 80 nM, about 1 nM toabout 75 nM, about 1 nM to about 70 nM, about 1 nM to about 65 nM, about1 nM to about 60 nM, about 1 nM to about 55 nM, about 1 nM to about 50nM, about 1 nM to about 45 nM, about 1 nM to about 40 nM, about 1 nM toabout 35 nM, about 1 nM to about 30 nM, about 1 nM to about 25 nM, about1 nM to about 20 nM, about 1 nM to about 15 nM, about 1 nM to about 10nM, about 1 nM to about 5 nM, about 2 nM to about 5 μM, about 2 nM toabout 2 μM, about 2 nM to about 1 μM, about 2 nM to about 500 nM, about2 nM to about 250 nM, about 2 nM to about 240 nM, about 2 nM to about230 nM, about 2 nM to about 220 nM, about 2 nM to about 210 nM, about 2nM to about 200 nM, about 2 nM to about 190 nM, about 2 nM to about 180nM, about 2 nM to about 170 nM, about 2 nM to about 160 nM, about 2 nMto about 150 nM, about 2 nM to about 140 nM, about 2 nM to about 130 nM,about 2 nM to about 120 nM, about 2 nM to about 110 nM, about 2 nM toabout 100 nM, about 2 nM to about 95 nM, about 2 nM to about 90 nM,about 2 nM to about 85 nM, about 2 nM to about 80 nM, about 2 nM toabout 75 nM, about 2 nM to about 70 nM, about 2 nM to about 65 nM, about2 nM to about 60 nM, about 2 nM to about 55 nM, about 2 nM to about 50nM, about 2 nM to about 45 nM, about 2 nM to about 40 nM, about 2 nM toabout 35 nM, about 2 nM to about 30 nM, about 2 nM to about 25 nM, about2 nM to about 20 nM, about 2 nM to about 15 nM, about 2 nM to about 10nM, about 2 nM to about 5 nM, about 4 nM to about 5 μM, about 4 nM toabout 2 μM, about 4 nM to about 1 μM, about 4 nM to about 500 nM, about4 nM to about 250 nM, about 4 nM to about 240 nM, about 4 nM to about230 nM, about 4 nM to about 220 nM, about 4 nM to about 210 nM, about 4nM to about 200 nM, about 4 nM to about 190 nM, about 4 nM to about 180nM, about 4 nM to about 170 nM, about 4 nM to about 160 nM, about 4 nMto about 150 nM, about 4 nM to about 140 nM, about 4 nM to about 130 nM,about 4 nM to about 120 nM, about 4 nM to about 110 nM, about 4 nM toabout 100 nM, about 4 nM to about 95 nM, about 4 nM to about 90 nM,about 4 nM to about 85 nM, about 4 nM to about 80 nM, about 4 nM toabout 75 nM, about 4 nM to about 70 nM, about 4 nM to about 65 nM, about4 nM to about 60 nM, about 4 nM to about 55 nM, about 4 nM to about 50nM, about 4 nM to about 45 nM, about 4 nM to about 40 nM, about 4 nM toabout 35 nM, about 4 nM to about 30 nM, about 4 nM to about 25 nM, about4 nM to about 20 nM, about 4 nM to about 15 nM, about 4 nM to about 10nM, about 4 nM to about 5 nM, about 5 nM to about 5 μM, about 5 nM toabout 2 μM, about 5 nM to about 1 μM, about 5 nM to about 500 nM, about5 nM to about 250 nM, about 5 nM to about 240 nM, about 5 nM to about230 nM, about 5 nM to about 220 nM, about 5 nM to about 210 nM, about 5nM to about 200 nM, about 5 nM to about 190 nM, about 5 nM to about 180nM, about 5 nM to about 170 nM, about 5 nM to about 160 nM, about 5 nMto about 150 nM, about 5 nM to about 140 nM, about 5 nM to about 130 nM,about 5 nM to about 120 nM, about 5 nM to about 110 nM, about 5 nM toabout 100 nM, about 5 nM to about 95 nM, about 5 nM to about 90 nM,about 5 nM to about 85 nM, about 5 nM to about 80 nM, about 5 nM toabout 75 nM, about 5 nM to about 70 nM, about 5 nM to about 65 nM, about5 nM to about 60 nM, about 5 nM to about 55 nM, about 5 nM to about 50nM, about 5 nM to about 45 nM, about 5 nM to about 40 nM, about 5 nM toabout 35 nM, about 5 nM to about 30 nM, about 5 nM to about 25 nM, about5 nM to about 20 nM, about 5 nM to about 15 nM, about 5 nM to about 10nM, about 10 nM to about 5 μM, about 10 nM to about 2 μM, about 10 nM toabout 1 μM, about 10 nM to about 500 nM, about 10 nM to about 250 nM,about 10 nM to about 240 nM, about 10 nM to about 230 nM, about 10 nM toabout 220 nM, about 10 nM to about 210 nM, about 10 nM to about 200 nM,about 10 nM to about 190 nM, about 10 nM to about 180 nM, about 10 nM toabout 170 nM, about 10 nM to about 160 nM, about 10 nM to about 150 nM,about 10 nM to about 140 nM, about 10 nM to about 130 nM, about 10 nM toabout 120 nM, about 10 nM to about 110 nM, about 10 nM to about 100 nM,about 10 nM to about 95 nM, about 10 nM to about 90 nM, about 10 nM toabout 85 nM, about 10 nM to about 80 nM, about 10 nM to about 75 nM,about 10 nM to about 70 nM, about 10 nM to about 65 nM, about 10 nM toabout 60 nM, about 10 nM to about 55 nM, about 10 nM to about 50 nM,about 10 nM to about 45 nM, about 10 nM to about 40 nM, about 10 nM toabout 35 nM, about 10 nM to about 30 nM, about 10 nM to about 25 nM,about 10 nM to about 20 nM, about 10 nM to about 15 nM, about 15 nM toabout 5 μM, about 15 nM to about 2 μM, about 15 nM to about 1 μM, about15 nM to about 500 nM, about 15 nM to about 250 nM, about 15 nM to about240 nM, about 15 nM to about 230 nM, about 15 nM to about 220 nM, about15 nM to about 210 nM, about 15 nM to about 200 nM, about 15 nM to about190 nM, about 15 nM to about 180 nM, about 15 nM to about 170 nM, about15 nM to about 160 nM, about 15 nM to about 150 nM, about 15 nM to about140 nM, about 15 nM to about 130 nM, about 15 nM to about 120 nM, about15 nM to about 110 nM, about 15 nM to about 100 nM, about 15 nM to about95 nM, about 15 nM to about 90 nM, about 15 nM to about 85 nM, about 15nM to about 80 nM, about 15 nM to about 75 nM, about 15 nM to about 70nM, about 15 nM to about 65 nM, about 15 nM to about 60 nM, about 15 nMto about 55 nM, about 15 nM to about 50 nM, about 15 nM to about 45 nM,about 15 nM to about 40 nM, about 15 nM to about 35 nM, about 15 nM toabout 30 nM, about 15 nM to about 25 nM, about 15 nM to about 20 nM,about 20 nM to about 5 μM, about 20 nM to about 2 μM, about 20 nM toabout 1 μM, about 20 nM to about 500 nM, about 20 nM to about 250 nM,about 20 nM to about 240 nM, about 20 nM to about 230 nM, about 20 nM toabout 220 nM, about 20 nM to about 210 nM, about 20 nM to about 200 nM,about 20 nM to about 190 nM, about 20 nM to about 180 nM, about 20 nM toabout 170 nM, about 20 nM to about 160 nM, about 20 nM to about 150 nM,about 20 nM to about 140 nM, about 20 nM to about 130 nM, about 20 nM toabout 120 nM, about 20 nM to about 110 nM, about 20 nM to about 100 nM,about 20 nM to about 95 nM, about 20 nM to about 90 nM, about 20 nM toabout 85 nM, about 20 nM to about 80 nM, about 20 nM to about 75 nM,about 20 nM to about 70 nM, about 20 nM to about 65 nM, about 20 nM toabout 60 nM, about 20 nM to about 55 nM, about 20 nM to about 50 nM,about 20 nM to about 45 nM, about 20 nM to about 40 nM, about 20 nM toabout 35 nM, about 20 nM to about 30 nM, about 20 nM to about 25 nM,about 25 nM to about 5 μM, about 25 nM to about 2 μM, about 25 nM toabout 1 μM, about 25 nM to about 500 nM, about 25 nM to about 250 nM,about 25 nM to about 240 nM, about 25 nM to about 230 nM, about 25 nM toabout 220 nM, about 25 nM to about 210 nM, about 25 nM to about 200 nM,about 25 nM to about 190 nM, about 25 nM to about 180 nM, about 25 nM toabout 170 nM, about 25 nM to about 160 nM, about 25 nM to about 150 nM,about 25 nM to about 140 nM, about 25 nM to about 130 nM, about 25 nM toabout 120 nM, about 25 nM to about 110 nM, about 25 nM to about 100 nM,about 25 nM to about 95 nM, about 25 nM to about 90 nM, about 25 nM toabout 85 nM, about 25 nM to about 80 nM, about 25 nM to about 75 nM,about 25 nM to about 70 nM, about 25 nM to about 65 nM, about 25 nM toabout 60 nM, about 25 nM to about 55 nM, about 25 nM to about 50 nM,about 25 nM to about 45 nM, about 25 nM to about 40 nM, about 25 nM toabout 35 nM, about 25 nM to about 30 nM, about 30 nM to about 5 μM,about 30 nM to about 2 μM, about 30 nM to about 1 μM, about 30 nM toabout 500 nM, about 30 nM to about 250 nM, about 30 nM to about 240 nM,about 30 nM to about 230 nM, about 30 nM to about 220 nM, about 30 nM toabout 210 nM, about 30 nM to about 200 nM, about 30 nM to about 190 nM,about 30 nM to about 180 nM, about 30 nM to about 170 nM, about 30 nM toabout 160 nM, about 30 nM to about 150 nM, about 30 nM to about 140 nM,about 30 nM to about 130 nM, about 30 nM to about 120 nM, about 30 nM toabout 110 nM, about 30 nM to about 100 nM, about 30 nM to about 95 nM,about 30 nM to about 90 nM, about 30 nM to about 85 nM, about 30 nM toabout 80 nM, about 30 nM to about 75 nM, about 30 nM to about 70 nM,about 30 nM to about 65 nM, about 30 nM to about 60 nM, about 30 nM toabout 55 nM, about 30 nM to about 50 nM, about 30 nM to about 45 nM,about 30 nM to about 40 nM, about 30 nM to about 35 nM, about 40 nM toabout 5 μM, about 40 nM to about 2 μM, about 40 nM to about 1 μM, about40 nM to about 500 nM, about 40 nM to about 250 nM, about 40 nM to about240 nM, about 40 nM to about 230 nM, about 40 nM to about 220 nM, about40 nM to about 210 nM, about 40 nM to about 200 nM, about 40 nM to about190 nM, about 40 nM to about 180 nM, about 40 nM to about 170 nM, about40 nM to about 160 nM, about 40 nM to about 150 nM, about 40 nM to about140 nM, about 40 nM to about 130 nM, about 40 nM to about 120 nM, about40 nM to about 110 nM, about 40 nM to about 100 nM, about 40 nM to about95 nM, about 40 nM to about 90 nM, about 40 nM to about 85 nM, about 40nM to about 80 nM, about 40 nM to about 75 nM, about 40 nM to about 70nM, about 40 nM to about 65 nM, about 40 nM to about 60 nM, about 40 nMto about 55 nM, about 40 nM to about 50 nM, about 40 nM to about 45 nM,about 50 nM to about 5 μM, about 50 nM to about 2 μM, about 50 nM toabout 1 μM, about 50 nM to about 500 nM, about 50 nM to about 250 nM,about 50 nM to about 240 nM, about 50 nM to about 230 nM, about 50 nM toabout 220 nM, about 50 nM to about 210 nM, about 50 nM to about 200 nM,about 50 nM to about 190 nM, about 50 nM to about 180 nM, about 50 nM toabout 170 nM, about 50 nM to about 160 nM, about 50 nM to about 150 nM,about 50 nM to about 140 nM, about 50 nM to about 130 nM, about 50 nM toabout 120 nM, about 50 nM to about 110 nM, about 50 nM to about 100 nM,about 50 nM to about 95 nM, about 50 nM to about 90 nM, about 50 nM toabout 85 nM, about 50 nM to about 80 nM, about 50 nM to about 75 nM,about 50 nM to about 70 nM, about 50 nM to about 65 nM, about 50 nM toabout 60 nM, about 50 nM to about 55 nM, about 60 nM to about 5 μM,about 60 nM to about 2 μM, about 60 nM to about 1 μM, about 60 nM toabout 500 nM, about 60 nM to about 250 nM, about 60 nM to about 240 nM,about 60 nM to about 230 nM, about 60 nM to about 220 nM, about 60 nM toabout 210 nM, about 60 nM to about 200 nM, about 60 nM to about 190 nM,about 60 nM to about 180 nM, about 60 nM to about 170 nM, about 60 nM toabout 160 nM, about 60 nM to about 150 nM, about 60 nM to about 140 nM,about 60 nM to about 130 nM, about 60 nM to about 120 nM, about 60 nM toabout 110 nM, about 60 nM to about 100 nM, about 60 nM to about 95 nM,about 60 nM to about 90 nM, about 60 nM to about 85 nM, about 60 nM toabout 80 nM, about 60 nM to about 75 nM, about 60 nM to about 70 nM,about 60 nM to about 65 nM, about 70 nM to about 5 μM, about 70 nM toabout 2 μM, about 70 nM to about 1 μM, about 70 nM to about 500 nM,about 70 nM to about 250 nM, about 70 nM to about 240 nM, about 70 nM toabout 230 nM, about 70 nM to about 220 nM, about 70 nM to about 210 nM,about 70 nM to about 200 nM, about 70 nM to about 190 nM, about 70 nM toabout 180 nM, about 70 nM to about 170 nM, about 70 nM to about 160 nM,about 70 nM to about 150 nM, about 70 nM to about 140 nM, about 70 nM toabout 130 nM, about 70 nM to about 120 nM, about 70 nM to about 110 nM,about 70 nM to about 100 nM, about 70 nM to about 95 nM, about 70 nM toabout 90 nM, about 70 nM to about 85 nM, about 70 nM to about 80 nM,about 70 nM to about 75 nM, about 80 nM to about 5 μM, about 80 nM toabout 2 μM, about 80 nM to about 1 μM, about 80 nM to about 500 nM,about 80 nM to about 250 nM, about 80 nM to about 240 nM, about 80 nM toabout 230 nM, about 80 nM to about 220 nM, about 80 nM to about 210 nM,about 80 nM to about 200 nM, about 80 nM to about 190 nM, about 80 nM toabout 180 nM, about 80 nM to about 170 nM, about 80 nM to about 160 nM,about 80 nM to about 150 nM, about 80 nM to about 140 nM, about 80 nM toabout 130 nM, about 80 nM to about 120 nM, about 80 nM to about 110 nM,about 80 nM to about 100 nM, about 80 nM to about 95 nM, about 80 nM toabout 90 nM, about 80 nM to about 85 nM, about 90 nM to about 5 μM,about 90 nM to about 2 μM, about 90 mM to about 1 μM, about 90 nM toabout 500 nM, about 90 nM to about 250 nM, about 90 nM to about 240 nM,about 90 nM to about 230 nM, about 90 nM to about 220 nM, about 90 nM toabout 210 nM, about 90 nM to about 200 nM, about 90 nM to about 190 nM,about 90 nM to about 180 nM, about 90 nM to about 170 nM, about 90 nM toabout 160 nM, about 90 nM to about 150 nM, about 90 nM to about 140 nM,about 90 nM to about 130 nM, about 90 nM to about 120 nM, about 90 nM toabout 110 nM, about 90 nM to about 100 nM, about 90 nM to about 95 nM,about 100 nM to about 5 μM, about 100 nM to about 2 μM, about 100 nM toabout 1 μM, about 100 nM to about 500 nM, about 100 nM to about 250 nM,about 100 nM to about 240 nM, about 100 nM to about 230 nM, about 100 nMto about 220 nM, about 100 nM to about 210 nM, about 100 nM to about 200nM, about 100 nM to about 190 nM, about 100 nM to about 180 nM, about100 nM to about 170 nM, about 100 nM to about 160 nM, about 100 nM toabout 150 nM, about 100 nM to about 140 nM, about 100 nM to about 130nM, about 100 nM to about 120 nM, about 100 nM to about 110 nM, about110 nM to about 5 μM, about 110 nM to about 2 μM, about 110 nM to about1 μM, about 110 nM to about 500 nM, about 110 nM to about 250 nM, about110 nM to about 240 nM, about 110 nM to about 230 nM, about 110 nM toabout 220 nM, about 110 nM to about 210 nM, about 110 nM to about 200nM, about 110 nM to about 190 nM, about 110 nM to about 180 nM, about HOnM to about 170 nM, about 110 nM to about 160 nM, about 110 nM to about150 nM, about 110 nM to about 140 nM, about 110 nM to about 130 nM,about 110 nM to about 120 nM, about 120 nM to about 5 μM, about 120 nMto about 2 μINA, about 120 nM to about 1 μM, about 120 nM to about 500nM, about 120 nM to about 250 nM, about 120 nM to about 240 nM, about120 nM to about 230 nM, about 120 nM to about 220 nM, about 120 nM toabout 210 nM, about 120 nM to about 200 nM, about 120 nM to about 190nM, about 120 nM to about 180 nM, about 120 nM to about 170 nM, about120 nM to about 160 nM, about 120 nM to about 150 nM, about 120 nM toabout 140 nM, about 120 nM to about 130 nM, about 130 nM to about 5 μM,about 130 nM to about 2 μM, about 130 nM to about 1 μM, about 130 nM toabout 500 nM, about 130 nM to about 250 nM, about 130 nM to about 240nM, about 130 nM to about 230 nM, about 130 nM to about 220 nM, about130 nM to about 210 nM, about 130 nM to about 200 nM, about 130 nM toabout 190 nM, about 130 nM to about 180 nM, about 130 nM to about 170nM, about 130 nM to about 160 nM, about 130 nM to about 150 nM, about130 nM to about 140 nM, about 140 nM to about 5 μM, about 140 nM toabout 2 μM, about 140 nM to about 1 μM, about 140 nM to about 500 nM,about 140 nM to about 250 nM, about 140 nM to about 240 nM, about 140 nMto about 230 nM, about 140 nM to about 220 nM, about 140 nM to about 210nM, about 140 nM to about 200 nM, about 140 nM to about 190 nM, about140 nM to about 180 nM, about 140 nM to about 170 nM, about 140 nM toabout 160 nM, about 140 nM to about 150 nM, about 150 nM to about 5 μM,about 150 nM to about 2 μM, about 150 nM to about 1 μM, about 150 nM toabout 500 nM, about 150 nM to about 250 nM, about 150 nM to about 240nM, about 150 nM to about 230 nM, about 150 nM to about 220 nM, about150 nM to about 210 nM, about 150 nM to about 200 nM, about 150 nM toabout 190 nM, about 150 nM to about 180 nM, about 150 nM to about 170nM, about 150 nM to about 160 nM, about 160 nM to about 5 about 160 nMto about 2 μM, about 160 nM to about 1 μM, about 160 nM to about 500 nM,about 160 nM to about 250 nM, about 160 nM to about 240 nM, about 160 nMto about 230 nM, about 160 nM to about 220 nM, about 160 nM to about 210nM, about 160 nM to about 200 nM, about 160 nM to about 190 nM, about160 nM to about 180 nM, about 160 nM to about 170 nM, about 170 nM toabout 5 μM, about 170 nM to about 2 μM, about 170 nM to about 1 about170 nM to about 500 nM, about 170 nM to about 250 nM, about 170 nM toabout 240 nM, about 170 nM to about 230 nM, about 170 nM to about 220nM, about 170 nM to about 210 nM, about 170 nM to about 200 nM, about170 nM to about 190 nM, about 170 nM to about 180 nM, about 180 nM toabout 5 μM, about 180 nM to about 2 μM, about 180 nM to about 1 μM,about 180 nM to about 500 nM, about 180 nM to about 250 nM, about 180 nMto about 240 nM, about 180 nM to about 230 nM, about 180 nM to about 220nM, about 180 nM to about 210 nM, about 180 nM to about 200 nM, about180 nM to about 190 nM, about 190 nM to about 5 μM, about 190 nM toabout 2 μM, about 190 nM to about 1 μM, about 190 nM to about 500 nM,about 190 nM to about 250 nM, about 190 nM to about 240 nM, about 190 nMto about 230 nM, about 190 nM to about 220 nM, about 190 nM to about 210nM, about 190 nM to about 200 nM, about 200 nM to about 5 μM, about 200nM to about 2 μM, about 200 nM to about 1 about 200 nM to about 500 nM,about 200 nM to about 250 nM, about 200 nM to about 240 nM, about 200 nMto about 230 nM, about 200 nM to about 220 nM, about 200 nM to about 210nM, about 210 nM to about 5 μM, about 210 nM to about 2 μM, about 210 nMto about 1 μM, about 210 nM to about 500 nM, about 210 nM to about 250nM, about 210 nM to about 240 nM, about 210 nM to about 230 nM, about210 nM to about 220 nM, about 220 nM to about 5 μM, about 220 nM toabout 2 μM, about 220 nM to about 1 μM, about 220 nM to about 500 nM,about 220 nM to about 250 nM, about 220 nM to about 240 nM, about 220 nMto about 230 nM, about 230 nM to about 5 μM, about 230 nM to about 2 μM,about 230 nM to about 1 μM, about 230 nM to about 500 nM, about 230 nMto about 250 nM, about 230 nM to about 240 nM, about 240 nM to about 5μM, about 240 nM to about 2 μM, about 240 nM to about 1 μM, about 240 nMto about 500 nM, about 240 nM to about 250 nM, about 250 nM to about 5about 250 nM to about 2 μM, about 250 nM to about 1 μM, about 250 nM toabout 500 nM, about 500 nM to about 5 about 500 nM to about 2 μM, about500 nM to about 1 μM, about 1 μM to about 5 μM, about 1 μM to about 2 orabout 2 μM to about 5 μM).

In some embodiments of any of the ABPCs described herein, the K_(D) ofthe first antigen-binding domain (and optionally, the secondantigen-binding domain, if present) at a pH of about 4.0 to about 6.5(e.g., any of the subranges of this range described herein) can begreater than 1 nM (e.g., between about 1 nM to about 1 mM, about 1 nM toabout 900 μM, about 1 nM to about 800 μM, about 1 nM to about 700 nM,about 1 nM to about 600 μM, about 1 nM to about 500 μM, about 1 nM toabout 400 μM, about 1 nM to about 300 nM, about 1 nM to about 200 μM,about 1 nM to about 100 nM, about 1 nM to about 90 μM, about 1 nM toabout 80 μM, about 1 nM to about 70 μM, about 1 nM to about 60 nM, about1 nM to about 50 μM, about 1 nM to about 40 about 1 nM to about 30 μM,about 1 nM to about 20 about 1 nM to about 10 μM, about 1 nM to about 5μM, about 1 nM to about 4 μM, about 1 nM to about 2 μM, about 1 nM toabout 1 μM, about 1 nM to about 900 nM, about 1 nM to about 800 nM,about 1 nM to about 700 nM, about 1 nM to about 600 nM, about 1 nM toabout 500 nM, about 1 nM to about 400 nM, about 1 nM to about 300 nM,about 1 nM to about 200 nM, about 1 nM to about 100 nM, about 1 nM toabout 90 nM, about 1 nM to about 80 nM, about 1 nM to about 70 nM, about1 nM to about 60 nM, about 1 nM to about 50 nM, about 1 nM to about 40nM, about 1 nM to about 30 nM, about 2 nM to about 1 mM, about 2 nM toabout 900 μM, about 2 nM to about 800 μM, about 2 nM to about 700 μM,about 2 nM to about 600 μM, about 2 nM to about 500 μM, about 2 nM toabout 400 μM, about 2 nM to about 300 μM, about 2 nM to about 200 μM,about 2 nM to about 100 μM, about 2 nM to about 90 μM, about 2 nM toabout 80 μM, about 2 nM to about 70 μM, about 2 nM to about 60 μM, about2 nM to about 50 μM, about 2 nM to about 40 μM, about 2 nM to about 30μM, about 2 nM to about 20 about 2 nM to about 10 μM, about 2 nM toabout 5 μM, about 2 nM to about 4 μM, about 2 nM to about 2 μM, about 2nM to about 1 μM, about 2 nM to about 900 nM, about 2 nM to about 800nM, about 2 nM to about 700 nM, about 2 nM to about 600 nM, about 2 nMto about 500 nM, about 2 nM to about 400 nM, about 2 nM to about 300 nM,about 2 nM to about 200 nM, about 2 nM to about 100 nM, about 2 nM toabout 90 nM, about 2 nM to about 80 nM, about 2 nM to about 70 nM, about2 nM to about 60 nM, about 2 nM to about 50 nM, about 2 nM to about 40nM, about 2 nM to about 30 nM, about 5 nM to about 1 mM, about 5 nM toabout 900 μM, about 5 nM to about 800 μM, about 5 nM to about 700 μM,about 5 nM to about 600 μM, about 5 nM to about 500 μM, about 5 nM toabout 400 μM, about 5 nM to about 300 μM, about 5 nM to about 200 μM,about 5 nM to about 100 μM, about 5 nM to about 90 μM, about 5 nM toabout 80 μM, about 5 nM to about 70 μM, about 5 nM to about 60 μM, about5 nM to about 50 nM, about 5 nM to about 40 μM, about 5 nM to about 30μM, about 5 nM to about 20 μM, about 5 nM to about 10 μM, about 5 nM toabout 5 μM, about 5 nM to about 4 μM, about 5 nM to about 2 μM, about 5nM to about 1 μM, about 5 nM to about 900 nM, about 5 nM to about 800nM, about 5 nM to about 700 nM, about 5 nM to about 600 nM, about 5 nMto about 500 nM, about 5 nM to about 400 nM, about 5 nM to about 300 nM,about 5 nM to about 200 nM, about 5 nM to about 100 nM, about 5 nM toabout 90 nM, about 5 nM to about 80 nM, about 5 nM to about 70 nM, about5 nM to about 60 nM, about 5 nM to about 50 nM, about 5 nM to about 40nM, about 5 nM to about 30 nM, about 10 nM to about 1 mM, about 10 nM toabout 900 nM, about 10 nM to about 800 nM, about 10 nM to about 700 nM,about 10 nM to about 600 μM, about 10 nM to about 500 μM, about 10 nM toabout 400 nM, about 10 nM to about 300 nM, about 10 nM to about 200 μM,about 10 nM to about 100 nM, about 10 nM to about 90 μM, about 10 nM toabout 80 μM, about 10 nM to about 70 μM, about 10 nM to about 60 about10 nM to about 50 μM, about 10 nM to about 40 μM, about 10 nM to about30 μM, about 10 nM to about 20 about 10 nM to about 10 μM, about 10 nMto about 5 μM, about 10 nM to about 4 μM, about 10 nM to about 2 μM,about 10 nM to about 1 μM, about 10 nM to about 900 nM, about 10 nM toabout 800 nM, about 10 nM to about 700 nM, about 10 nM to about 600 nM,about 10 nM to about 500 nM, about 10 nM to about 400 nM, about 10 nM toabout 300 nM, about 10 nM to about 200 nM, about 10 nM to about 100 nM,about 10 nM to about 90 nM, about 10 nM to about 80 nM, about 10 nM toabout 70 nM, about 10 nM to about 60 nM, about 10 nM to about 50 nM,about 10 nM to about 40 nM, about 10 nM to about 30 nM, about 20 nM toabout 1 mM, about 20 nM to about 900 μM, about 20 nM to about 800 μM,about 20 nM to about 700 μM, about 20 nM to about 600 μM, about 20 nM toabout 500 μM, about 20 nM to about 400 μM, about 20 nM to about 300 μM,about 20 nM to about 200 about 20 nM to about 100 μM, about 20 nM toabout 90 nM, about 20 nM to about 80 μM, about 20 nM to about 70 μM,about 20 nM to about 60 nM, about 20 nM to about 50 μM, about 20 nM toabout 40 μM, about 20 nM to about 30 μM, about 20 nM to about 20 μM,about 20 nM to about 10 μM, about 20 nM to about 5 μM, about 20 nM toabout 4 μM, about 20 nM to about 2 μM, about 20 nM to about 1 μM, about20 nM to about 900 nM, about 20 nM to about 800 nM, about 20 nM to about700 nM, about 20 nM to about 600 nM, about 20 nM to about 500 nM, about20 nM to about 400 nM, about 20 nM to about 300 nM, about 20 nM to about200 nM, about 20 nM to about 100 nM, about 20 nM to about 90 nM, about20 nM to about 80 nM, about 20 nM to about 70 nM, about 20 nM to about60 nM, about 20 nM to about 50 nM, about 20 nM to about 40 nM, about 20nM to about 30 nM; about 1 μM to about 1 mM, about 1 μM to about 900 μM,about 1 μM to about 800 μM, about 1 μM to about 700 μM, about 1 μM toabout 600 μM, about 1 μM to about 500 μM, about 1 μM to about 400 μM,about 1 μM to about 300 nM, about 1 μM to about 200 about 1 μM to about100 μM, about 1 μM to about 90 μM, about 1 μM to about 80 μM, about 1 μMto about 70 μM, about 1 μM to about 60 μM, about 1 μM to about 50 μM;about 1 μM to about 400 μM, about 1 μM to about 30 μM, about 1 μM toabout 20 μM, about 1 μM to about 10 μM, about 1 μM to about 5 μM, about1 μM to about 4 μM, about 1 μM to about 3 about 1 μM to about 2 μM,about 2 μM to about 1 mM, about 2 μM to about 900 μM about 2 μM to about800 μM, about 2 μM to about 700 μM, about 2 μM to about 600 μM, about 2μM to about 500 μM, about 2 μM to about 400 μM, about 2 μM to about 300μM, about 2 μM to about 200 μM, about 2 μM to about 100 μM, about 2 μMto about 90 μM, about 2 μM to about 80 μM, about 2 μM to about 70 μM,about 2 μM to about 60 μM, about 2 μM to about 50 μM, about 2 μM toabout 40 μM, about 2 μM to about 30 μM, about 2 μM to about 20 μM, about2 to about 10 μM, about 2 μM to about 5 μM, about 2 μM to about 4 μM,about 2 μM to about 3 μM, about 5 μM to about 1 mM, about 5 μM to about900 μM, about 5 μM to about 800 μM, about 5 μM to about 700 μM, about 5μM to about 600 μM; about 5 μM to about 500 μM, about 5 μM to about 400μM, about 5 μM to about 300 μM; about 5 μM to about 200 μM, about 5 μMto about 100 μM, about 5 μM to about 90 μM, about 5 μM to about 80 μM,about 5 μM to about 70 μM, about 5 μM to about 60 μM, about 5 μM toabout 50 μM, about 5 μM to about 40 μM, about 2 μM to about 30 μM, about5 μM to about 20 μM, about 5 μM to about 10 μM, about 10 μM to about 1mM, about 10 μM to about 900 μM, about 10 μM to about 800 μM, about 10μM to about 700 μM, about 10 μM to about 600 μM, about 10 μM to about500 μM, about 10 μM to about 400 μM, about 10 μM to about 300 μM, about10 μM to about 200 μM, about 10 μM to about 100 μM, about 10 μM to about90 μM, about 10 to about 80 μM, about 10 μM to about 70 about 10 μM toabout 60 μM, about 10 to about 50 μM, about 10 μM to about 40 μM, about10 μM to about 30 μM, about 10 11M to about 20 μM, about 20 μM to about1 mM, about 20 μM to about 900 μM, about 20 μM to about 800 μM, about 20μM to about 700 μM; about 20 μM to about 600 μM, about 20 μM to about500 μM, about 20 μM to about 400 μM, about 20 μM to about 300 μM, about20 μM to about 200 μM, about 20 μM to about 100 μM, about 20 μM to about90 μM, about 20 μM to about 80 μM, about 20 μM to about 70 μM, about 20μM to about 60 μM, about 20 μM to about 50 μM, about 20 μM to about 40μM, about 20 μM to about 30 μM, about 30 μM to about 1 mM, about 30 μMto about 900 μM, about 30 μM to about 800 μM, about 30 μM to about 700μM, about 30 μM to about 600 μM, about 30 μM to about 500 μM, about 30μM to about 400 μM, about 30 μM to about 300 μM, about 30 μM to about200 μM, about 30 μM to about 100 μM, about 30 μM to about 90 μM, about30 μM to about 80 μM, about 30 μM to about 70 μM, about 30 μM to about60 μM, about 30 μM to about 50 μM, about 30 μM to about 40 μM, about 40μM to about 1 mM, about 40 μM to about 900 μM, about 40 μM to about 800μM, about 40 μM to about 700 μM, about 40 μM to about 600 μM, about 40μM to about 500 μM, about 40 μM to about 400 μM, about 40 μM to about300 μM, about 40 μM to about 200 μM, about 40 μM to about 100 μM, about40 μM to about 90 μM, about 40 μM to about 80 μM, about 40 μM to about70 μM, about 40 μM to about 60 μM, about 40 μM to about 50 μM, about 50μM to about 1 mM, about 50 μM to about 900 μM, about 50 μM to about 800μM, about 50 μM to about 700 μM, about 50 μM to about 600 μM, about 50μM to about 500 μM, about 50 μM to about 400 μM, about 50 μM to about300 μM, about 50 μM to about 200 μM; about 50 μM to about 100 μM, about50 μM to about 90 μM, about 50 μM to about 80 μM, about 50 μM to about70 μM, about 50 μM to about 60 μM, about 60 μM to about 1 mM, about 60μM to about 900 μM, about 60 μM to about 800 μM, about 60 μM to about700 μM, about 60 μM to about 600 μM, about 60 μM to about 500 μM, about60 μM to about 400 μM, about 60 μM to about 300 μM, about 60 μM to about200 μM, about 60 μM to about 100 μM, about 60 μM to about 90 μM, about60 μM to about 80 μM, about 60 μM to about 70 μM, about 70 μM to about 1mM, about 70 μM to about 900 μM, about 70 μM to about 800 μM, about 70μM to about 700 μM, about 70 μM to about 600 μM, about 70 μM to about500 μM, about 70 μM to about 400 μM, about 70 μM to about 300 μM, about70 μM to about 200 μM, about 70 μM to about 100 μM, about 70 μM to about90 μM, about 70 μM to about 80 μM, about 80 μM to about 1 mM, about 80μM to about 900 μM, about 80 μM to about 800 μM, about 80 μM to about700 μM, about 80 μM to about 600 μM, about 80 μM to about 500 μM, about80 μM to about 400 μM, about 80 μM to about 300 μM, about 80 μM to about200 μM, about 80 μM to about 100 μM, about 80 μM to about 90 μM, about90 μM to about 1 mM, about 90 μM to about 900 μM, about 90 μM to about800 μA& about 90 μM to about 700 μM, about 90 μM to about 600 μM, about90 μM to about 500 μM, about 90 μM to about 400 μM, about 90 μM to about300 μM, about 90 μM to about 200 μM, about 90 μM to about 100 μM, about100 μM to about 1 mM, about 100 μM to about 900 μM, about 100 μM toabout 800 μM, about 100 μM to about 700 μM, about 100 μM to about 600μM, about 100 μM to about 500 μM, about 100 μM to about 400 μM, about100 μM to about 300 μM, about 100 μM to about 200 μM, about 200 μM toabout 1 mM, about 200 μM to about 900 μM, about 200 μM to about 800 μM;about 200 μM to about 700 μM, about 200 μM to about 600 μM, about 200 μMto about 500 μM, about 200 μM to about 400 μM, about 200 μM to about 300μM, about 300 μM to about 1 mM, about 300 μM to about 900 μM, about 300μM to about 800 μM, about 300 μM to about 700 μM, about 300 μM to about600 μM, about 300 μM to about 500 μM, about 300 μM to about 400 μM,about 400 μM to about 1 mM, about 400 μM to about 900 μM, about 400 μMto about 800 μM, about 400 mM to about 700 μM, about 400 μM to about 600μM, about 400 μM to about 500 μM, about 500 μM to about 1 mM, about 500μM to about 900 μM, about 500 μM to about 800 μM, about 500 μM to about700 μM, about 500 μM to about 600 μM, about 600 μM to about 1 mM, about600 μM to about 900 μM, about 600 μM to about 800 μM, about 600 μM toabout 700 μM, about 700 μM to about 1 mM, about 700 μM to about 900 μM,about 700 μM to about 800 μM, about 800 μM to about 1 mM, about 800 μMto about 900 μM, or about 900 μM to about 1 mM).

A variety of different methods known in the art can be used to determinethe K_(D) values of any of the antigen-binding protein constructsdescribed herein (e.g., an electrophoretic mobility shift assay, afilter binding assay, surface plasmon resonance, a biomolecular bindingkinetics assay, in vitro binding assay on antigen-expressing cells,etc.).

In some examples of any of the ABPCs described herein, the half-life ofthe ABPC in vivo is decreased (e.g., a detectable decrease) (e.g., atleast a 1% decrease, at least a 5% decrease, at least a 10% decrease, atleast a 15% decrease, at least a 20% decrease, at least a 25% decrease,at least a 30% decrease, at least a 35% decrease, at least a 40%decrease, at least a 45% decrease, at least a 50% decrease, at least a55% decrease, at least a 60% decrease, at least a 65% decrease, at leasta 70% decrease, at least a 75% decrease, at least a 80% decrease, atleast a 85% decrease, at least a 90% decrease, at least a 95% decrease,or at least a 99% decrease, or about a 1% decrease to about a 99%decrease, about a 1% decrease to about a 95% decrease, about a 1%decrease to about a 90% decrease, about a 1% decrease to about a 85%decrease, about a 1% decrease to about a 80% decrease, about a 1%decrease to about a 75% decrease, about a 1% decrease to about a 70%decrease, about a 1% decrease to about a 65% decrease, about a 1%decrease to about a 60% decrease, about a 1% decrease to about a 55%decrease, about a 1% decrease to about a 509/0 decrease, about a 1%decrease to about a 45% decrease, about a 1% decrease to about a 409/0decrease, about a 1% decrease to about a 35% decrease, about a 1%decrease to about a 30% decrease, about a 1% decrease to about a 25%decrease, about a 1% decrease to about a 20% decrease, about a 1%decrease to about a 15% decrease, about a 1% decrease to about a 10%decrease, about a 1% decrease to about a 5% decrease, about a 5%decrease to about a 99% decrease, about a 5% decrease to about a 95%decrease, about a 5% decrease to about a 90% decrease, about a 5%decrease to about a 85% decrease, about a 5% decrease to about a 80%decrease, about a 5% decrease to about a 75% decrease, about a 5%decrease to about a 70% decrease, about a 5% decrease to about a 65%decrease, about a 5% decrease to about a 60% decrease, about a 5%decrease to about a 55% decrease, about a 5% decrease to about a 50%decrease, about a 5% decrease to about a 45% decrease, about a 5%decrease to about a 40% decrease, about a 5% decrease to about a 35%decrease, about a 5% decrease to about a 30% decrease, about a 5%decrease to about a 25% decrease, about a 5% decrease to about a 20%decrease, about a 5% decrease to about a 15% decrease, about a 5%decrease to about a 10% decrease, about a 10% decrease to about a 99%decrease, about a 10% decrease to about a 95% decrease, about a 10%decrease to about a 90% decrease, about a 10% decrease to about a 85%decrease, about a 10% decrease to about a 80% decrease, about a 10%decrease to about a 75% decrease, about a 10% decrease to about a 70%decrease, about a 10% decrease to about a 65% decrease, about a 10%decrease to about a 60% decrease, about a 10% decrease to about a 55%decrease, about a 10% decrease to about a 50% decrease, about a 10%decrease to about a 45% decrease, about a 10% decrease to about a 40%decrease, about a 10% decrease to about a 35% decrease, about a 10%decrease to about a 30% decrease, about a 10% decrease to about a 25%decrease, about a 10% decrease to about a 20% decrease, about a 10%decrease to about a 15% decrease, about a 15% decrease to about a 99%decrease, about a 15% decrease to about a 95% decrease, about a 15%decrease to about a 90% decrease, about a 15% decrease to about a 85%decrease, about a 15% decrease to about a 80% decrease, about a 15%decrease to about a 75% decrease, about a 15% decrease to about a 70%decrease, about a 15% decrease to about a 65% decrease, about a 15%decrease to about a 60% decrease, about a 15% decrease to about a 55%decrease, about a 15% decrease to about a 50% decrease, about a 15%decrease to about a 45% decrease, about a 15% decrease to about a 40%decrease, about a 15% decrease to about a 35% decrease, about a 15%decrease to about a 30% decrease, about a 15% decrease to about a 25%decrease, about a 15% decrease to about a 20% decrease, about a 20%decrease to about a 99% decrease, about a 20% decrease to about a 95%decrease, about a 20% decrease to about a 90% decrease, about a 20%decrease to about a 85% decrease, about a 20% decrease to about a 80%decrease, about a 20% decrease to about a 75% decrease, about a 20%decrease to about a 70% decrease, about a 20% decrease to about a 65%decrease, about a 20% decrease to about a 60% decrease, about a 20%decrease to about a 55% decrease, about a 20% decrease to about a 50%decrease, about a 20% decrease to about a 45% decrease, about a 20%decrease to about a 40% decrease, about a 20% decrease to about a 35%decrease, about a 20% decrease to about a 30% decrease, about a 20%decrease to about a 25% decrease, about a 25% decrease to about a 99%decrease, about a 25% decrease to about a 95% decrease, about a 25%decrease to about a 90% decrease, about a 25% decrease to about a 85%decrease, about a 25% decrease to about a 80% decrease, about a 25%decrease to about a 75% decrease, about a 25% decrease to about a 70%decrease, about a 25% decrease to about a 65% decrease, about a 25%decrease to about a 60% decrease, about a 25% decrease to about a 55%decrease, about a 25% decrease to about a 50% decrease, about a 25%decrease to about a 45% decrease, about a 25% decrease to about a 40%decrease, about a 25% decrease to about a 35% decrease, about a 25%decrease to about a 30% decrease, about a 30% decrease to about a 99%decrease, about a 30% decrease to about a 95% decrease, about a 30%decrease to about a 90% decrease, about a 30% decrease to about a 85%decrease, about a 30% decrease to about a 80% decrease, about a 30%decrease to about a 75% decrease, about a 30% decrease to about a 70%decrease, about a 30% decrease to about a 65% decrease, about a 30%decrease to about a 60% decrease, about a 30% decrease to about a 55%decrease, about a 30% decrease to about a 50% decrease, about a 30%decrease to about a 45% decrease, about a 30% decrease to about a 40%decrease, about a 30% decrease to about a 35% decrease, about a 35%decrease to about a 99% decrease, about a 35% decrease to about a 95%decrease, about a 35% decrease to about a 90% decrease, about a 35%decrease to about a 85% decrease, about a 35% decrease to about a 80%decrease, about a 35% decrease to about a 75% decrease, about a 35%decrease to about a 70% decrease, about a 35% decrease to about a 65%decrease, about a 35% decrease to about a 60% decrease, about a 35%decrease to about a 55% decrease, about a 35% decrease to about a 50%decrease, about a 35% decrease to about a 45% decrease, about a 35%decrease to about a 40% decrease, about a 40% decrease to about a 99%decrease, about a 40% decrease to about a 95% decrease, about a 40%decrease to about a 90% decrease, about a 40% decrease to about a 85%decrease, about a 40% decrease to about a 80% decrease, about a 40%decrease to about a 75% decrease, about a 40% decrease to about a 70%decrease, about a 40% decrease to about a 65% decrease, about a 40%decrease to about a 60% decrease, about a 40% decrease to about a 55%decrease, about a 40% decrease to about a 50% decrease, about a 40%decrease to about a 45% decrease, about a 45% decrease to about a 99%decrease, about a 45% decrease to about a 95% decrease, about a 45%decrease to about a 90% decrease, about a 45% decrease to about a 85%decrease, about a 45% decrease to about a 80% decrease, about a 45%decrease to about a 75% decrease, about a 45% decrease to about a 709/0decrease, about a 45% decrease to about a 65% decrease, about a 45%decrease to about a 60% decrease, about a 45% decrease to about a 55%decrease, about a 45% decrease to about a 50% decrease, about a 50%decrease to about a 99% decrease, about a 50% decrease to about a 95%decrease, about a 50% decrease to about a 90% decrease, about a 50%decrease to about a 85% decrease, about a 50% decrease to about a 80%decrease, about a 50% decrease to about a 75% decrease, about a 50%decrease to about a 70% decrease, about a 50% decrease to about a 65%decrease, about a 50% decrease to about a 60% decrease, about a 50%decrease to about a 55% decrease, about a 55% decrease to about a 99%decrease, about a 55% decrease to about a 95% decrease, about a 55%decrease to about a 90% decrease, about a 55% decrease to about a 85%decrease, about a 55% decrease to about a 80% decrease, about a 55%decrease to about a 75% decrease, about a 55% decrease to about a 70%decrease, about a 55% decrease to about a 65% decrease, about a 55%decrease to about a 60% decrease, about a 60% decrease to about a 99%decrease, about a 60% decrease to about a 95% decrease, about a 60%decrease to about a 90% decrease, about a 60% decrease to about a 85%decrease, about a 60% decrease to about a 80% decrease, about a 60%decrease to about a 75% decrease, about a 60% decrease to about a 70%decrease, about a 60% decrease to about a 65% decrease, about a 65%decrease to about a 99% decrease, about a 65% decrease to about a 95%decrease, about a 65% decrease to about a 90% decrease, about a 65%decrease to about a 85% decrease, about a 65% decrease to about a 80%decrease, about a 65% decrease to about a 75% decrease, about a 65%decrease to about a 70% decrease, about a 70% decrease to about a 99%decrease, about a 70% decrease to about a 95% decrease, about a 70%decrease to about a 90% decrease, about a 70% decrease to about a 85%decrease, about a 70% decrease to about a 80% decrease, about a 70%decrease to about a 75% decrease, about a 75% decrease to about a 99%decrease, about a 75% decrease to about a 95% decrease, about a 75%decrease to about a 90% decrease, about a 75% decrease to about a 85%decrease, about a 75% decrease to about a 80% decrease, about a 80%decrease to about a 99% decrease, about a 80% decrease to about a 959/0decrease, about a 80% decrease to about a 90% decrease, about a 80%decrease to about a 85% decrease, about a 85% decrease to about a 99%decrease, about a 85% decrease to about a 95% decrease, about a 85%decrease to about a 90% decrease, about a 90% decrease to about a 99%decrease, about a 90% decrease to about a 95% decrease, or about a 95%decrease to about a 99% decrease) as compared to the half-life of acontrol ABPC (e.g., any of the exemplary control ABPCs describedherein).

Conjugation

In some embodiments, the ABPCs provided herein can be conjugated to adrug (e.g., a chemotherapeutic drug, a small molecule), a toxin, or aradioisotope. Non-limiting examples of drugs, toxins, and radioisotopes(e.g., known to be useful for the treatment of cancer) are known in theart.

In some embodiments, at least one polypeptide of any of the ABPCsdescribed herein is conjugated to the toxin, the radioisotope, or thedrug via a cleavable linker. In some embodiments, the cleavable linkerincludes a protease cleavage site. In some embodiments, the cleavablelinker is cleaved on the ABPC once it is transported to the lysosome orlate endosome by the target mammalian cell. In some embodiments,cleavage of the linker functionally activates the drug or toxin.

In some embodiments, at least one polypeptide of any of the ABPCsdescribed herein is conjugated to the toxin, the radioisotope, or thedrug via a non-cleavable linker. In some embodiments, the conjugatedtoxin, radioisotope, or drug is released during lysosomal and/or lateendosomal degradation of the ABPC.

Non-limiting examples of cleavable linkers include: hydrazone linkers,peptide linkers, disulfide linkers, and thioether linkers. See, e.g.,Carter et al., Cancer J. 14(3):154-169, 2008; Sanderson et al., Clin.Cancer Res. 11(2 Pt1: 843-852, 2005; Chari et al., Acc. Chem. Res.41(1):98-107, 2008; Oflazoglu et al., Clin. Cancer Res. 14(19):6171-6180, 2008; and Lu et al., Int. J. Mol. Sci. 17(4): 561, 2016.

Non-limiting examples of non-cleavable linkers include: maleimidealkane-linkers and meleimide cyclohexane linker (MMC) (see, e.g., thosedescribed in McCombs et al., AAPS J. 17(2):339-351, 2015).

In some embodiments, any of the ABPCs described herein is cytotoxic orcytostatic to the target mammalian cell.

Expression of an Antigen-Binding Protein Construct in a Cell

Also provided herein are methods of generating a recombinant cell thatexpresses an ABPC (e.g., any of the ABPCs described herein) thatinclude: introducing into a cell a nucleic acid encoding the ABPC toproduce a recombinant cell; and culturing the recombinant cell underconditions sufficient for the expression of the ABPC. In someembodiments, the introducing step includes introducing into a cell anexpression vector including a nucleic acid encoding the ABPC to producea recombinant cell.

Any of the ABPCs described herein can be produced by any cell, e.g., aeukaryotic cell or a prokaryotic cell. As used herein, the term“eukaryotic cell” refers to a cell having a distinct, membrane-boundnucleus. Such cells may include, for example, mammalian (e.g., rodent,non-human primate, or human), insect, fungal, or plant cells. In someembodiments, the eukaryotic cell is a yeast cell, such as Saccharomycescerevisiae, In some embodiments, the eukaryotic cell is a highereukaryote, such as mammalian, avian, plant, or insect cells. As usedherein, the term “prokaryotic cell” refers to a cell that does not havea distinct, membrane-bound nucleus. In some embodiments, the prokaryoticcell is a bacterial cell.

Methods of culturing cells are well known in the art. Cells can bemaintained in vitro under conditions that favor proliferation,differentiation, and growth. Briefly, cells can be cultured bycontacting a cell (e.g., any cell) with a cell culture medium thatincludes the necessary growth factors and supplements to support cellviability and growth.

Methods of introducing nucleic acids and expression vectors into a cell(e.g., a eukaryotic cell) are known in the art. Non-limiting examples ofmethods that can be used to introduce a nucleic acid into a cell includelipofection, transfection, electroporation, microinjection, calciumphosphate transfection, dendrimer-based transfection, cationic polymertransfection, cell squeezing, sonoporation, optical transfection,impalection, hydrodynamic delivery, magnetofection, viral transduction(e.g., adenoviral and lentiviral transduction), and nanoparticletransfection.

Provided herein are methods that further include isolation of the ABPCsfrom a cell (e.g., a eukaryotic cell) using techniques well-known in theart (e.g., ammonium sulfate precipitation, polyethylene glycolprecipitation, ion-exchange chromatography (anion or cation),chromatography based on hydrophobic interaction, metal-affinitychromatography, ligand-affinity chromatography, and size exclusionchromatography).

Methods of Treatment

Provided herein are methods of treating a cancer characterized by havinga population of cancer cells that have FOLR1 or an epitope of FOLR1presented on their surface, that include: administering atherapeutically effective amount of any of the pharmaceuticalcompositions described herein or any of the ABPCs described herein to asubject identified as having a cancer characterized by having thepopulation of cancer cells.

Also provided herein are methods of reducing the volume of a tumor in asubject, wherein the tumor is characterized by having a population ofcancer cells that have FOLR1 or an epitope of FOLR1 presented on theirsurface, that include: administering a therapeutically effective amountof any of the pharmaceutical compositions described herein or any of theABPCs described herein to a subject identified as having a cancercharacterized by having the population of cancer cells. In someembodiments of any of the methods described herein, the volume of atleast one (e.g., 1, 2, 3, 4, or 5) tumor (e.g., solid tumor) or tumorlocation (e.g., a site of metastasis) is reduced (e.g., a detectablereduction) by at least 1%, at least 2%, at least 3%, at least 4%, atleast 5%, at least 6%, at least 8%, at least 10%, at least 12%, at least14%, at least 16%, at least 18%, at least 20%, at least 22%, at least24%, at least 26%, at least 28%, at least 30%, at least 35%, at least40%, at least 45%, at least 50%, at least 55%, at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least90%, at least 95%, or at least 99%) reduced as compared to the size ofthe at least one tumor (e.g., solid tumor) before administration of theABPC.

Also provided herein are methods of inducing cell death in a cancer cellin a subject, wherein the cancer cell has FOLR1 or an epitope of FOLR1presented on its surface, that include: administering a therapeuticallyeffective amount of any of the pharmaceutical compositions of describedherein or any of the ABPCs described herein to a subject identified ashaving a cancer characterized as having the population of cancer cells.In some embodiments, the cell death that is induced is necrosis. In someembodiments, the cell death that is induced is apoptosis.

In some embodiments of any of the methods described herein, the canceris a primary tumor.

In some embodiments of any of the methods described herein, the canceris a metastasis. In some embodiments of any of the methods describedherein, the cancer is a non-T-cell-infiltrating tumor. In someembodiments of any of the methods described herein, the cancer is aT-cell-infiltrating tumor.

Provided herein are methods of decreasing the risk of developing ametastasis or decreasing the risk of developing an additional metastasisin a subject having a cancer, wherein the cancer is characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface, that include: administering atherapeutically effective amount of any of the pharmaceuticalcompositions of described herein or any of the ABPCs described herein toa subject identified as having a cancer characterized as having thepopulation of cancer cells. In some embodiments, the risk of developinga metastasis or the risk of developing an additional metastasis isdecreased (e.g., a detectable decrease) by at least 1%, by at least 2%,at least 3%, at least 4%, at least 5%, at least 6%, at least 8%, atleast 10%, at least 12%, at least 14%, at least 16%, at least 18%, atleast 20%, at least 25%, at least 30%, at least 35%, at least 40%, atleast 45%, at least 50%, at least 55%, at least 60%, at least 65%, atleast 70%, at least 75%, at least 80%, at least 85%, at least 90%, atleast 95%, or at least 99% in the subject as compared to the risk of asubject having a similar cancer, but administered no treatment or atreatment that does not include the administration of any of the ABPCsdescribed herein.

In some embodiments of any of the methods described herein, the canceris a non-T-cell-infiltrating tumor. In some embodiments of any of themethods described herein, the cancer is a T-cell-infiltrating tumor. Insome embodiments of any of the methods described herein, the cellularcompartment is part of the endosomal/lysosomal pathway. In someembodiments of any of the methods described herein, the cellularcompartment is an endosome.

The term “subject” refers to any mammal. In some embodiments, thesubject or “subject suitable for treatment” may be a canine (e.g., adog), feline (e.g., a cat), equine (e.g., a horse), ovine, bovine,porcine, caprine, primate, e.g., a simian (e.g., a monkey (e.g.,marmoset, baboon), or an ape (e.g., a gorilla, chimpanzee, orangutan, orgibbon) or a human; or rodent (e.g., a mouse, a guinea pig, a hamster,or a rat). In some embodiments, the subject or “subject suitable fortreatment” may be a non-human mammal, especially mammals that areconventionally used as models for demonstrating therapeutic efficacy inhumans (e.g., murine, lapine, porcine, canine or primate animals) may beemployed.

As used herein, treating includes reducing the number, frequency, orseverity of one or more (e.g., two, three, four, or five) signs orsymptoms of a cancer in a patient having a cancer (e.g., any of thecancers described herein). For example, treatment can reducing cancerprogression, reduce the severity of a cancer, or reduce the risk ofre-occurrence of a cancer in a subject having the cancer.

Provided herein are methods of inhibiting the growth of a solid tumor ina subject (e.g., any of the subjects described herein) that includeadministering to the subject a therapeutically effective amount of anyof the ABPCs described herein or any of the pharmaceutical compositionsdescribed herein (e.g., as compared to the growth of the solid tumor inthe subject prior to treatment or the growth of a similar solid tumor ina different subject receiving a different treatment or receiving notreatment).

In some embodiments of any of the methods described herein, the growthof a solid tumor is primary growth of a solid tumor. In some embodimentsof any of the methods described herein, the growth of a solid tumor isrecurrent growth of a solid tumor. In some embodiments of any of themethods described herein, the growth of a solid tumor is metastaticgrowth of a solid tumor. In some embodiments, treatment results in abouta 1% decrease to about 99% decrease (or any of the subranges of thisrange described herein) in the growth of a solid tumor in the subject(e.g., as compared to the growth of the solid tumor in the subject priorto treatment or the growth of a similar solid tumor in a differentsubject receiving a different treatment or receiving no treatment). Thegrowth of a solid tumor in a subject can be assessed by a variety ofdifferent imaging methods, e.g., positron emission tomograph, X-raycomputed tomography, computed axial tomography, and magnetic resonanceimaging.

Also provided herein are methods of decreasing the risk of developing ametastasis or developing an additional metastasis over a period of timein a subject identified as having a cancer (e.g., any of the exemplarycancers described herein) that include administering to the subject atherapeutically effective amount of any of the proteins described hereinor any of the pharmaceutical compositions described herein (e.g., ascompared to a subject having a similar cancer and receiving a differenttreatment or receiving no treatment). In some embodiments of any of themethods described herein, the metastasis or additional metastasis is oneor more to a bone, lymph nodes, brain, lung, liver, skin, chest wallincluding bone, cartilage and soft tissue, abdominal cavity,contralateral breast, soft tissue, muscle, bone marrow, ovaries, adrenalglands, and pancreas.

In some embodiments of any of the methods described herein, the periodof time is about 1 month to about 3 years (e.g., about 1 month to about2.5 years, about 1 month to about 2 years, about 2 months to about 1.5years, about 1 month to about 1 year, about 1 month to about 10 months,about 1 month to about 8 months, about 1 month to about 6 months, about1 month to about 5 months, about 1 month to about 4 months, about 1month to about 3 months, about 1 month to about 2 months, about 2 monthsto about 3 years, about 2 months to about 2.5 years, about 2 months toabout 2 years, about 2 months to about 1.5 years, about 2 months toabout 1 year, about 2 months to about 10 months, about 2 months to about8 months, about 2 months to about 6 months, about 2 months to about 5months, about 2 months to about 4 months, about 2 months to about 3months, about 3 months to about 3 years, about 3 months to about 2.5years, about 3 months to about 2 years, about 3 months to about 1.5years, about 3 months to about 1 year, about 3 months to about 10months, about 3 months to about 8 months, about 3 months to about 6months, about 3 months to about 5 months, about 3 months to about 4months, about 4 months to about 3 years, about 4 months to about 2.5years, about 4 months to about 2 years, about 4 months to about 1.5years, about 4 months to about 1 year, about 4 months to about 10months, about 4 months to about 8 months, about 4 months to about 6months, about 4 months to about 5 months, about 5 months to about 3years, about 5 months to about 2.5 years, about 5 months to about 2years, about 5 months to about 1.5 years, about 5 months to about 1year, about 5 months to about 10 months, about 5 months to about 8months, about 5 months to about 6 months, about 6 months to about 3years, about 6 months to about 2.5 years, about 6 months to about 2years, about 6 months to about 1.5 years, about 6 months to about 1year, about 6 months to about 10 months, about 6 months to about 8months, about 8 months to about 3 years, about 8 months to about 2.5years, about 8 months to about 2 years, about 8 months to about 1.5years, about 8 months to about 1 year, about 8 months to about 10months, about 10 months to about 3 years, about 10 months to about 2.5years, about 10 months to about 2 years, about 10 months to about 1.5years, about 10 months to about 1 year, about 1 year to about 3 years,about 1 year to about 2.5 years, about 1 year to about 2 years, about 1year to about 1.5 years, about 1.5 years to about 3 years, about 1.5years to about 2.5 years, about 1.5 years to about 2 years, about 2years to about 3 years, about 2 years to about 2.5 years, or about 2.5years to about 3 years).

In some embodiments, the risk of developing a metastasis or developingan additional metastasis over a period of time in a subject identifiedas having a cancer is decreased by about 1% to about 99% (e.g., or anyof the subranges of this range described herein), e.g., as compared tothe risk in a subject having a similar cancer receiving a differenttreatment or receiving no treatment.

Non-limiting examples of cancer include: acute lymphoblastic leukemia(ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, analcancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor,bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchialtumor, Burkitt Lymphoma, carcinoma of unknown primary origin, cardiactumor, cervical cancer, chordoma, chronic lymphocytic leukemia (CLL),chronic myelogenous leukemia (CML), chronic myeloproliferative neoplasm,colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-celllymphoma, ductal carcinoma, embryonal tumor, endometrial cancer,ependymoma, esophageal cancer, esthesioneuroblastoma, fibroushistiocytoma, Ewing sarcoma, eye cancer, germ cell tumor, gallbladdercancer, gastric cancer, gastrointestinal carcinoid tumor,gastrointestinal stromal tumor, gestational trophoblastic disease,glioma, head and neck cancer, hairy cell leukemia, hepatocellularcancer, histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer,intraocular melanoma, islet cell tumor, Kaposi sarcoma, kidney cancer,Langerhans cell histiocytosis, laryngeal cancer, leukemia, lip and oralcavity cancer, liver cancer, lobular carcinoma in situ, lung cancer,lymphoma, macroglobulinemia, malignant fibrous histiocytoma, melanoma,Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancerwith occult primary, midline tract carcinoma involving NUT gene, mouthcancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosisfungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferativeneoplasm, nasal cavity and para-nasal sinus cancer, nasopharyngealcancer, neuroblastoma, non-Hodgkin lymphoma, non-small cell lung cancer,oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer,papillomatosis, paraganglioma, parathyroid cancer, penile cancer,pharyngeal cancer, pheochromocytomas, pituitary tumor, pleuropulmonaryblastoma, primary central nervous system lymphoma, prostate cancer,rectal cancer, renal cell cancer, renal pelvis and ureter cancer,retinoblastoma, rhabdoid tumor, salivary gland cancer, Sezary syndrome,skin cancer, small cell lung cancer, small intestine cancer, soft tissuesarcoma, spinal cord tumor, stomach cancer, T-cell lymphoma, teratoidtumor, testicular cancer, throat cancer, thymoma and thymic carcinoma,thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvarcancer, and Wilms' tumor. Additional examples of cancer are known in theart.

In some embodiments, the patient is further administered one or moreadditional therapeutic agents (e.g., one or more of a chemotherapeuticagent, a recombinant cytokine or interleukin protein, a kinaseinhibitor, and a checkpoint inhibitor). In some embodiments, the one ormore additional therapeutic agents is administered to the patient atapproximately the same time as any of the ABPCs described herein areadministered to the patient. In some embodiments, the one or moreadditional therapeutic agents are administered to the patient after theadministration of any of the ABPCs described herein to the patient. Insome embodiments, the one or more additional therapeutic agents areadministered to the patient before the administration of any of theABPCs described herein to the patient. In some embodiments of any of themethods described herein, the cancer is a solid cancer (e.g., breastcancer, prostate cancer, or non-small cell lung cancer).

Compositions

Also provided herein are compositions (e.g., pharmaceuticalcompositions) that include at least one of any of the ABPCs describedherein. In some embodiments, the compositions (e.g., pharmaceuticalcompositions) can be disposed in a sterile vial or a pre-loaded syringe.

In some embodiments, the compositions (e.g., pharmaceuticalcompositions) are formulated for different routes of administration(e.g., intravenous, subcutaneous, intramuscular, or intratumoral). Insome embodiments, the compositions (e.g., pharmaceutical compositions)can include a pharmaceutically acceptable carrier (e.g., phosphatebuffered saline). Single or multiple administrations of any of thepharmaceutical compositions described herein can be given to a subjectdepending on, for example: the dosage and frequency as required andtolerated by the patient. A dosage of the pharmaceutical compositionshould provide a sufficient quantity of the ABPC to effectively treat orameliorate conditions, diseases, or symptoms.

Also provided herein are methods of treating a subject having a cancer(e.g., any of the cancers described herein) that include administering atherapeutically effective amount of at least one of any of thecompositions or pharmaceutical compositions provided herein.

Kits

Also provided herein are kits that include any of the ABPCs describedherein, any of the compositions described herein, or any of thepharmaceutical compositions described herein. In some embodiments, thekits can include instructions for performing any of the methodsdescribed herein. In some embodiments, the kits can include at least onedose of any of the compositions (e.g., pharmaceutical compositions)described herein. In some embodiments, the kits can provide a syringefor administering any of the pharmaceutical compositions describedherein.

Protein Constructs

Also provided are protein constructs (PCs) that include: a firstantigen-binding domain that is capable of specifically binding FOLR1 oran epitope of FOLR1 presented on the surface of a target mammalian cell,where: (a) the dissociation rate of the first antigen-binding domain ata pH of about 7.0 to about 8.0 (or any of the subranges of this rangedescribed herein) is faster than the dissociation rate at a pH of about4.0 to about 6.5 (or any of the subranges of this range describedherein); and/or (b) the dissociation constant (K_(D)) of the firstantigen-binding domain at a pH of about 7.0 to about 8.0 (or any of thesubranges of this range) is greater than the K_(D) at a pH of about 4.0to about 6.5.

Also provided herein are pharmaceutical compositions including any ofthe PCs described herein. Also provided herein are methods of treating asubject in need thereof that include administering a therapeuticallyeffective amount of any of the PCs described herein to the subject.

Methods of Improving pH Dependence of an Antigen-Binding ProteinConstruct

Also provided herein are methods of improving pH dependence of anantigen-binding protein construct, the method comprises providing astarting antigen-binding protein construct comprising an antigen-bindingdomain and introducing one or more histidine amino acid substitutionsinto one or more CDRs of the antigen-binding domain in the startingantigen-binding protein construct, wherein the method results in thegeneration of an antigen-binding protein construct having one or bothof: (a) an increased (e.g., at least a 0.1-fold increase to about a100-fold increase, or any of the subranges of this range describedherein) ratio of the dissociation rate of the antigen-binding domain ata pH of about 4.0 to about 6.5 to the dissociation rate at a pH of about7.0 to about 8.0, as compared to the starting antigen-binding proteinconstruct, and (b) an increased (e.g., at least a 0.1-fold increase toabout a 100-fold increase, or any of the subranges of this rangedescribed herein) ratio the dissociation constant (K_(D)) of theantigen-binding domain at a pH of about 4.0 to about 6.5 to the K_(D) ata pH of about 7.0 to about 8.0, as compared to the startingantigen-binding protein construct.

The invention is further described in the following examples, which donot limit the scope of the invention described in the claims.

EXAMPLES Example 1. Generation of FOLR1 Binders and Engineering of pHBinding Dependence

pH-engineered ABPCs specific for FOLR1 are generated using two methods.In the first approach, published monoclonal antibodies against FOLR1 areused as a starting template for introduction of additional mutationsthat allow engineering of pH-dependent binding to FOLR1 and i) enhancedendolysosomal accumulation of a conjugated toxin, as well as ii)enhanced FOLR1 recycling to the cell surface. The second approachinvolves discovery of de novo ABPCs specific for FOLR1 via antibodydisplay methods from naive libraries or libraries with defined CDRcompositions and screening under conditions designed for selection ofpH-engineered ABPCs specific for FOLR1. In either case, histidineresidues play an important role in engineering pH-dependent bindingproteins. Histidine residues are at least partially protonated at a pHbelow 6.5 owing to its pKa of 6.0. Therefore, if a histidine side chainin an antigen-binding domain participates in an electrostatic bindinginteraction with its antigen it will start to turn positively charged ata pH at or below 6.5. This could either weaken or enhance the bindingaffinity of the interaction at a pH below 6.5, based on thecorresponding charge of and interactions with the antigen epitope. Thus,systematic introduction of histidines into antibody complementaritydetermining regions (CDRs) in an antibody or other binder library (e.g.,an scFv library) can be used to identify substitutions that will affectan antigen-binding domain's interaction with an antigen at lower pHvalues. The first approach therefore involves histidine-scanning ofvariable region sequences of published monoclonal antibodies to identifypH-dependent variants.

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding [Altwerger G et al (2018) “In Vitro and In Vivo Activity ofIMGN853, an Antibody—Drug Conjugate Targeting Folate Receptor AlphaLinked to DM4, in Biologically Aggressive Endometrial Cancers” MolecularCancer Therapeutics 7(5): 1003-1011]. Briefly, for a subset of theantibody sequences, CDRs in each chain are identified using the methodsdescribed by Kabat et al (Kabat et al. (1992) Sequences of Proteins ofImmunological Interest (DIANE publishing) and IMGT (Lefranc MP(1999)“The IMGT unique numbering for Immunoglobulins, T cell receptors andIg-like domains” The Immunologist 7, 132-136), and for each CDR,residues falling under either or both Kabat and IMGT CDR definitionswere called as CDR residues. To engineer pH-dependent sequence variants,individual amino acid residues within the heavy chain and/or light chainCDRs are systematically substituted with a histidine, one at a time. Incases where the starting CDR residue is a histidine, it is mutated to analanine. Antibody variants with only one histidine or alanine mutationin a heavy/light chain CDR are generated by co-transfection of Expi293cells with a) one heavy chain or light chain sequence variant, and b)the corresponding starting ABPC (e.g., the starting FOLR1-bindingmonoclonal antibody) light chain or heavy chain, respectively, usingmethods known to the art. After allowing for a period of proteinexpression, cell culture supernatants are collected, quantified, and thepH dependence of the variant is evaluated using biolayer interferometry(BLI) or other methods known to the art. Briefly, cell culturesupernatants are normalized to an antibody expression level of 50 μg/mL,and captured on an anti-human Fc sensor (Forte Bio). A baseline isestablished using 1× kinetics buffer (Forte Bio), and the sensor isassociated with 100 nM of FOLR1 in 1× PBS at pH 7.4 for 300 sec togenerate an association curve. In the dissociation phase, theantibody-antigen complex on the sensor is exposed to 1×PBS at either pH5.5 or pH 7.4 for 300-500 sec. Association and dissociation phase curvesare examined for the starting ABPC antibody and each correspondingantibody variant at pH 5.5 and pH 7.4 to inform on two criteria: a)enhanced dissociation (i.e., higher k_(off) values) at pH 5.5 due tohistidine or alanine substitution compared to the starting ABPC, and b)reduced dissociation at pH 7.4 (i.e., lower k_(off) values) compared topH 5.5 in the antibody variant itself and with the starting ABPC.Variants that show either enhanced dissociation at pH 5.5 or reduceddissociation at pH 7.4 or both are selected for further analysis. It isalso noted that while some histidine and alanine mutations obliterateFOLR1 binding, others are tolerated with little (e.g., less than 1-foldchange in KD or dissociation rate) or no change in FOLR1 bindingkinetics. Especially because histidine is a large, positively chargedamino acid, these histidine variants and alanine variants with no changeare noted as positions that may tolerate a wide range of mutations andlead to antibodies with different sequence but similar bindingproperties, a designation that is not otherwise apparent. The variantsselected for further analysis are expressed at a larger scale andpurified using protein A affinity chromatography. Binding kinetics(k_(on) and k_(off)) of the purified starting ABPC and variantantibodies are measured at pH 5.5 and pH 7.4 using Biacore (GEHealthcare). The ratio of the antibody's rate of dissociation (k_(off)at pH 7.4 divided by k_(off) at pH 5.5) is also used as a quantitativeassessment of pH-dependent binding; similarly, the dissociation constantK_(D) is calculated at both pH 5.5 and pH 7.4 as k_(off) divided byk_(on) and the ratio of the antibody's dissociation constant (K_(D) atpH 7.4 divided by K_(D) at pH 5.5) is also used as a quantitativeassessment of pH-dependent binding. Antibodies with a rate ofdissociation ratio less than that of the starting ABPC and/or adissociation constant ratio less than that of the starting ABPC areselected for further assessment of combinatorial substitutions.Favorable histidine and/or alanine amino acid positions can also becombined to enhance pH dependence; this can be done by, e.g.,combinatorially or rationally combining histidine and/or alaninesubstitutions on a given heavy or light chain that individually improvepH dependence, by, e.g., combinatorially or rationally combiningmodified heavy and light chains such that histidine and/or alaninesubstitutions are present on both chains, or combinations thereof. Suchcombinatorial variants are generated and tested/analyzed fordifferential pH dependence using the methods and protocols describedherein, or others known to the art. Antibody variants that have thelowest rate of dissociation ratios and/or dissociation constant ratiosare selected as candidates for further analysis (hereafter referred toas “pH-engineered ABPCs specific for FOLR1”).

The second method for selection of pH-engineered ABPCs specific forFOLR1 involves either screening libraries to identify de novopH-dependent ABPCs specific for FOLR1 or ABPCs that could serve astemplates for engineering pH-dependent binding as described herein. Twotypes of libraries can be used for these selections: naive phage/yeastdisplay antibody libraries (e.g., Fab, scFv, VHH, VL, or others known tothe art) or phage/yeast display libraries where CDRs have been mutatedto express a subset of amino acid residues. Libraries are screenedagainst soluble recombinant FOLR1 extracellular domains using methodsknown to the art with positive selection for variants that bind weakly(e.g., are eluted from beads) at pH 5.0 and bind strongly (e.g., arebound to beads) at pH 7.4. Three rounds of selections are performed. Thefinal round of binders are screened using ELISA for binding to humanFOLR1 and cyno FOLR1 and mouse FOLR1 or via mean fluorescence intensityin flow cytometric analysis. If more binders with cyno or murinecross-reactivity are desired, the final selection round can instead beperformed on cyno FOLR1 or murine FOLR1. Selected binding proteins aresubcloned into mammalian expression vectors and expressed as either fullIgG proteins or Fc fusions in Expi293 cells. BLI analysis is performedas described herein for selection of pH-dependent binder variants andconfirmed using Biacore.

Example 2. In Vitro Demonstration of pH-Dependent Binding to FOLR1,pH-Dependent Release of FOLR1, Enhanced Endolysosomal Delivery in FOLR1+Cells, and Increased FOLR1 Antigen Density in FOLR1+ Cells afterExposure to pH-Engineered ABPCs Specific for FOLR1 as Compared toControl ABPCs Specific for FOLR1

As discussed herein, pH-engineered ABPCs specific for FOLR1 exhibit thedesirable property of decreased FOLR1 binding at acidic pH (e.g., pH5.0, pH 5.5), but enhanced binding at higher pH (e.g., pH 7.4), whichenhances their accumulation in endolysosomes under physiologicalconditions.

pH-Dependent Binding to FOLR1 on Cells

To demonstrate that pH-engineered ABPCs specific for FOLR1 binds cellsurface FOLR1 at neutral pH, a cell surface binding assay is performed.A panel of human cells that are FOLR1+ is assembled (e.g., KB, Igrov,Ovcar-3). Methods of identifying and quantifying gene expression (e.g.,FOLR1) for a given cell line are known to the art, and include, e.g.,consulting the Cancer Cell Line Encyclopedia (CCLE;https://portals.broadinstitute.org/ccle) to ascertain the expressionlevel and/or mutation status of a given gene in a tumor cell line),rtPCR, microarray, or RNA-Seq analysis, or cell staining with antibodiesknown in the art (e.g. R&D Systems FOLR1 Antibody, Cat #MAB5646 orInvitrogen FOLR1 Antibody, Cat #548908 for FOLR1). Cells are seeded atapproximately 5-10,000 per well in 150 μL of pH 7.4 culture medium andincubated at 37° C. for 5 minutes at several doses (e.g., a two-folddilution series) from 1 pM to 1 μM with one of the following antibodies:a known, control ABPC specific for FOLR1 (e.g., an antibody,mirvetuximab, or STRO-002, or Farletuzumab), the pH-engineered ABPCspecific for FOLR1, and an appropriate negative isotype control mAb(e.g., Biolegend Purified Human IgG1 Isotype Control RecombinantAntibody, Cat #403501). Prior to the onset of the experiment, thebinding properties of all antibodies are validated using methods knownto the art. Following the 5 minute incubation, cells are fixed with 4%formaldehyde (20 min at room temperature) and incubated with anappropriate fluorophore-labeled secondary antibody (e.g., ThermoFisherMouse anti-Human IgG1 Fc Secondary Antibody, Alexa Fluor 488, Cat#A-10631) for 60 minutes. Unbound reagents are washed with a series ofPBS washes, and the cell panels are imaged using confocal microscopy.Upon analysis of the images, significant fluorescence can be observed onthe surface of cells bound with the known, control ABPC specific forFOLR1 as well as the pH-engineered ABPC specific for FOLR1, but littlesurface binding can be observed for the isotype negative control. Toisolate the effect of pH on surface binding, the same experiment isrepeated twice, with the primary antibody incubation taking place atsequentially lower pH (e.g., pH 6.5 and 5.5 and 5.0). Analysis of theresulting confocal microscopy images can show significant fluorescenceon the surface of cells bound with all mAbs tested, excepting theisotype negative control, and that this fluorescence decreases for thepH-engineered ABPC specific for FOLR1 as the pH decreases.Alternatively, cells are analyzed for mean fluorescent intensity by flowcytometry using methods known in the art. A dissociation constant KD oncells at neutral pH of the antibodies analyzed is determined bynonlinear regression methods known in the art (e.g., a Scatchard plot).Taken together, the results can show that the pH engineering processresults in the creation of a pH-engineered ABPC specific for FOLR1 thatis pH-dependent in its binding properties and that it more effectivelybinds at neutral pH as compared to more acidic pH. Other methods ofassessing the pH dependence of the pH-engineered ABPCs specific forFOLR1 are known in the art and include, e.g., using flow cytometry tomeasure ABPC surface binding.

pH-Dependent Release of FOLR1 on Cells

To demonstrate that pH-engineered ABPCs specific for FOLR1 are capableof releasing FOLR1 at low pH after binding at a neutral pH, a variant ofthe cell surface binding assay described above is performed usingmethods known to the art (e.g., as generally described in Gera N. (2012)PLoS ONE 7(11): e48928). Briefly, an appropriate FOLR1+ cell line(passage number less than 25) is harvested and 50,000 cells per well areplated in a U-Bottomed 96-well microplate. Three conditions are tested;binding and secondary staining at pH 7.4, binding and secondary stainingat pH 5.0, and binding at pH 7.4 followed by release at pH 5.0 for 30minutes and secondary staining at pH 7.4. Both pH-engineered ABPCsspecific for FOLR1 as well as a control ABPC specific for FOLR1 aretested. The cells are washed two times with 200 μL of FACS buffer (lxPBS containing 3% Fetal Bovine Serum) at either pH 7.4 or 5.0 dependingon the condition being tested. The purified protein samples are dilutedinto FACS buffer of the appropriate pH and added to the cells andallowed to bind for one hour on ice. After incubation with the primaryantibodies the pH 7.4 and pH 5.0 conditions are washed twice as before,and then 100 μl of secondary rat anti-human Fc AF488 (BioLegend 410706)or other appropriate antibody, diluted 1:50, or anti Myc-Tag mousemAb-AF488 (Cell Signaling Technologies 2279S) diluted 1:50 is added inFACS buffer of the appropriate pH, and incubated for 30 minutes on ice.The pH 5.0 release condition is washed twice with FACS buffer pH 7.4 andthen resuspended in 100 μl of FACS buffer pH 5.0 and incubated on icefor 30 minutes, followed by secondary staining in FACS buffer pH 7.4 asdescribed for the other conditions. The plates are washed twice asbefore and resuspended in 1% paraformaldehyde in the appropriate FACSbuffer to fix them for flow cytometry analysis. All conditions are readon a flow cytometer (Accuri C6, BD Biosciences). Binding is observed asa shift in the FL1 signal (as a mean fluorescence intensity) versussecondary alone. Upon analysis of the data, it can be determined thatboth the pH-engineered ABPC specific for FOLR1 as well as the controlABPC specific for FOLR1 effectively bind the surface of FOLR1+ cells atneutral pH, but the pH-engineered ABPC specific for FOLR1 binds poorlyat pH 5.0; similarly, it can be determined that the pH-engineered ABPCspecific for FOLR1 binds effectively at pH 7.4, but thenreleases/unbinds FOLR1 at pH 5.0.

Enhanced Endolysosomal Delivery in FOLR1+ Cells of pH-Engineered ABPCsSpecific for FOLR1 as Compared to Control ABPCs Specific for FOLR1(pHrodo)

To verify and demonstrate that ABPCs specific for FOLR1 achieveendolysosomal localization following cellular uptake, an internalizationassay is performed using methods known to the art (e.g., Mahmutefendicet al., Int. J. Biochem. Cell Bio., 2011). Briefly, as described herein,a panel of human cells that express FOLR1 highly is assembled usingmethods known to the art. Cells are plated, washed three times with PBS,and incubated at 37 degrees C. for 60 minutes in media at neutral pH,with added concentrations of 2 micrograms per milliliter of a known,control ABPC specific for FOLR1 (e.g., as described herein), thepH-engineeredABPC specific for FOLR1, and an appropriate negativeisotype control mAb (e.g., as described herein). In a subset of cells,validation of antibody internalization and endosomal localization isperformed using methods known to the art; e.g., cells are fixed in 4%formaldehyde as described herein, permeabilized using TWEEN 20 or othermethods known to the art (Jamur M C et al (2010) Permeabilization ofcell membranes, Methods Mol Biol. 588:63-6), additionally stained withan endosomal marker, e.g., a fluorescent RAB11 antibody (RAB11 Antibody,Alexa Fluor 488, 3H18L5, ABfinity™ Rabbit Monoclonal), stained with anappropriate fluorescently labeled anti-human secondary antibody (e.g.,as described herein), and imaged using confocal fluorescence microscopy,as described herein. Analysis of the confocal images can be used to showthat both the pH-engineered ABPC specific for FOLR1 as well as thecontrol ABPC specific for FOLR1 are internalized and accumulate in theendolysosomes.

To demonstrate that pH-engineered ABPCs specific for FOLR1 achieveenhanced endolysosomal accumulation relative to a control ABPC specificfor FOLR1, a pHrodo-based internalization assay is performed using botha known, control ABPC specific for FOLR1 (e.g., as described herein) aswell as the pH-engineered ABPC specific for FOLR1. The assay makes useof pHrodo™ iFL (P36014, ThermoFisher), a dye whose fluorescenceincreases with decreasing pH, such that its level of fluorescenceoutside the cell at neutral pH is lower than its level of fluorescenceinside the acidic pH environment of endolysosomes. Briefly, anappropriate FOLR1+ cell line (less than passage 25) is suspended in itsrecommended media (e.g., by cell banks or cell bank databases ATCC,DSMZ, or ExPASy Cellosaurus) and plated in a 24-well plate at a densityof 2,000,000 cells/mL, 1 mL per well. While keeping the cells on ice, 1mL of 2× pHrodo iFL-labeled antibody (prepared in accordance with themanufacturer's instructions) is added to each well, the well ispipetted/mixed five times, and the plate is incubated in alight-protected environment for 45 minutes, on ice. An identical butseparate plate is also incubated on ice that is meant as ano-internalization negative control. Following this incubation, theexperimental plate is moved to a 37 degree C. incubator, the negativecontrol plate is kept on ice to slow or block internalization, andsamples are taken at designated time points to create an internalizationtime course. Samples are placed into a U-bottom 96-well plate, andinternalization is quenched via addition of 200 μL/well of ice-cold FACSbuffer. The plates are spun down at 2000×g for 2 minutes, resuspended in200 μL ice-cold FACS buffer, spun down again, and resuspended in FACSbuffer a second time. Finally, the samples are loaded into a flowcytometer for read-out of cellular pHrodo fluorescence using excitationand emission wavelengths consistent with the excitation and emissionmaxima of the pHrodo iFL Red dye (566 nm and 590 nm, respectively). Uponcompletion of the flow cytometry experiment and analysis of the data, itcan be observed that cells treated with the pH-engineered ABPC specificfor FOLR1 have a higher pHrodo iFL signal relative to a known, controlABPC specific for FOLR1, indicating that pH-engineered ABPCs specificfor FOLR1 achieve enhanced endolysosomal accumulation relative to acontrol ABPC specific for FOLR1.

Alternatively, to demonstrate that pH-engineered ABPCs specific forFOLR1 achieve enhanced endolysosomal accumulation relative to a controlABPC specific for FOLR1, a variation of the above-described experimentis performed. FOLR1+ cells are plated, washed three times with PBS, andincubated at 37 degrees C. for 60 minutes in media at neutral pH withadded concentrations of 2 μg/mL of either pH-engineered ABPC specificfor FOLR1 or control ABPC specific for FOLR1. Following incubation,cells are washed three times with PBS, fixed and permeabilized, andstained with a panel of appropriately selected antibodies that bind lateendosomal markers as well as lysosomes (e.g., RAB7, and LAMP1; CellSignaling Technology, Endosomal Marker Antibody Sampler Kit 412666;AbCam, Anti-LAMP2 antibody [GL2A7], ab13524). After primary antibodystaining, cells are stained with an appropriate mixture of fluorescentlylabeled secondary antibodies (e.g., Goat Anti-Human IgG (H&L) SecondaryAntibody (Alexa Fluor 647) Cat #A-21445, and Abcam Goat Anti-Rabbit IgGH&L (Alexa Fluor 488), Cagab150077), imaged using confocal fluorescencemicroscopy, and regions of co-localization of signal from FOLR1-specificantibodies and endosomal markers are visualized and quantified. Uponanalysis of the data, it can be revealed that there is increasedco-localization of endolysosmal and FOLR1-specific antibody signal inwells treated with the pH-engineered ABPCs specific for FOLR1 ascompared to wells treated with control ABPC specific for FOLR1, and canthereby demonstrate that pH-engineered ABPCs specific for FOLR1 achieveenhanced endolysosomal accumulation relative to control ABPC specificfor FOLR1.

Increased FOLR1 Antigen Density in FOLR1+ Cells after Exposure topH-Engineered ABPCs Specific for FOLR1 as Compared to Control ABPCsSpecific for FOLR1

To demonstrate that treatment of cells with the pH-engineered ABPCsspecific for FOLR1 does not result in a detectable reduction of thelevel of FOLR1 on the surface of cells exposed to the pH-engineeredABPCs specific for FOLR1, or that said treatment results in less of areduction of the level of FOLR1 on the surface of cells exposed to thepH-engineered ABPC specific for FOLR1 versus a control ABPC specific forFOLR1, an antigen density study is performed using flow cytometry.Briefly, 4.0×10{circumflex over ( )}5 cells that express FOLR1 areplated per well in a 96-well plate in 100 μL media. Cells are treatedwith a titration from 1 pM to 1 μM of i) pH-engineered ABPCs specificfor FOLR1, ii) a first control ABPC specific for FOLR1, iii) anappropriate isotype control, and iv) an untreated control. Cells areincubated for 2 hours at 37° C., at which point all cells are incubatedwith 200 nM of a fluorophore-labeled second control ABPC specific forFOLR1 (e.g., as described herein) which has a different epitope (asdetermined by, e.g., competitive binding studies on cells) than eitherthe first control ABPC specific for FOLR1 or the pH-engineered ABPCsspecific for FOLR1 for 30 minutes at 4° C. Following this 30-minuteincubation, the mean fluorescence intensity (MFI) of all cells is readout using, e.g., flow cytometry, using methods known to one of ordinaryskill in the art. In parallel, a quantitative standard curve that can beused to quantify the presence of FOLR1 on the surface of treated cellsas a function of MFI is generated using a commercially availablequantification kit (e.g., BD Biosciences PE Phycoerythrin FluorescenceQuantitation Kit, catalog #340495); the quantitative standard curve iscreated by following the manufacturer's instructions. Other methods ofdetermining the absolute number of FOLR1 on the cell surface are knownin the art and include, e.g., use of radioisotopically labeled reagents.Upon analysis of the data, it can be revealed that at least one antibodyconcentration, cells treated with a control ABPC specific for FOLR1experience a reduction of the level of FOLR1 on their surface, whereascells treated with pH-engineered ABPCs specific for FOLR1 experience asignificantly smaller reduction or no reduction at all, both relative tothe isotype and untreated controls.

Example 3. Conjugation of pH-Engineered and Control ABPCs Specific forFOLR1 to Cytotoxic Drugs

An antigen-binding protein construct conjugate (ADC) is made comprisingthe FOLR1-binding IgG (hereafter, FOLR1-IgG) described herein linked tomonomethyl auristatin E (MMAE) via a valine-citrulline (vc) linker(hereafter, FOLR1-IgG-DC). Conjugation of the antigen-binding proteinconstruct with vcMMAE begins with a partial reduction of the FOLR1-IgGfollowed by reaction with maleimidocaproyl-Val-Cit-PABC-MMAE (vcMMAE).The FOLR1-IgG (20 mg/mL) is partially reduced by addition of TCEP (molarequivalents of TCEP:mAb is 2:1) followed by incubation at 0° C.overnight. The reduction reaction is then warmed to 20° C. To conjugateall of the thiols, vcMMAE is added to a final vcMMAE:reduced Cys molarratio of 1:15. The conjugation reaction is carried out in the presenceof 10% v/v of DMSO and allowed to proceed at 20° C. for 60 minutes.

After the conjugation reaction, excess free N(acetyl)-Cysteine (2equivalents vs. vcMMAE charge) is added to quench unreacted vcMMAE toproduce the Cys-Val-Cit-MMAE adduct. The Cys quenching reaction isallowed to proceed at 20° C. for approximately 30 minutes. TheCys-quenched reaction mixture is purified as per below. The aboveconjugation method can also be used to conjugate maleimidocaproylmonomethylauristatin F LmcMMAF) to an antigen-binding protein construct.

The FOLR1-IgG-DC is purified using a batch purification method. Thereaction mixture is treated with the appropriate amount of water washedBu-HIC resin (ToyoPearl; Tosoh Biosciences), i.e., seven weights ofresin is added to the mixture. The resin/reaction mixture is stirred forthe appropriate time, and monitored by analytical hydrophobicinteraction chromatography for removal of drug conjugate products,filtered through a coarse polypropylene filter, and washed by two bedvolumes of a buffer (0.28 M sodium chloride, 7 mM potassium phosphate,pH 7). The combined filtrate and rinses are combined and analyzed forproduct profile by HIC HPLC. The combined filtrate and rinses are bufferexchanged by ultrafiltration/diafiltration (UF/DF) to 15 mM histidine,pH 6 with 10 diavolumes 15 nM histidine buffer.

A similar protocol can be used to conjugate DNA toxins such as SG3249and SGD-1910 to FOLR1-IgG (see Tiberghien A C et al (2016) Design andSynthesis of Tesirine, a Clinical Antibody—Drug ConjugatePyrrolobenzodiazepine Dimer Payload, ACS Med Chem Lett 7:983-987).Briefly, for SG3249, FOLR1-IgG (15 mg, 100 nanomoles) is diluted into13.5 mL of a reduction buffer containing 10 mM sodium borate pH 8.4, 2.5mM EDTA and a final antibody concentration of 1.11 mg/mL. A 10 mMsolution of TCEP is added (1.5 molar equivalent/antibody, 150 nanomoles,15 microliters) and the reduction mixture is heated at +37° C. for 1.5hours in an incubator. After cooling down to room temperature, SG3249 isadded as a DMSO solution (5 molar equivalent/antibody, 500 nanomoles, in1.5 mL DMSO). The solution is mixed for 1.25 hours at room temperature,then the conjugation is quenched by addition of N-acetyl cysteine (1micromole, 100 microliters at 10 mM), and injected into an AKTA™ PureFPLC using a GE Healthcare HiLoad™ 26/600 column packed with Superdex200 PG, and eluted with 2.6 mL/min of sterile-filteredphosphate-buffered saline (PBS). Fractions corresponding to theFOLR1-IgG-DC monomer peak are pooled, concentrated using a 15 mL AmiconUltracell 50 KDa MWCO spin filter, analysed and sterile-filtered. UHPLCanalysis on a Shimadzu Prominence system using a Phenomenex Aeris 3.6uXB-C18 150×2.1 mm column eluting with a gradient of water andacetonitrile on a reduced sample of FOLR1-IgG-DC at 280 nm and 330 nm(SG3249 specific) can show a mixture of light and heavy chains attachedto several molecules of SG3249, consistent with a drug-per-antibodyratio (DAR) of 1 to 4 molecules of SG3249 per antibody. UHPLC analysison a Shimadzu Prominence system using a Phenomenex Yarra 3u SEC-3000 300mm×4.60 mm column eluting with sterile-filtered SEC buffer containing200 mM potassium phosphate pH 6.95, 250 mM potassium chloride and 10%isopropanol (v/v) on a sample of FOLR1-IgG-DC at 280 nm can show amonomer purity of over 90% with no impurity detected. UHPLC SEC analysisallows determination of final FOLR1-IgG-DC yield of greater than 30%.

Alternatively, methods to conjugate toxins to antibodies via lysineresidues are known in the art (e.g., see Catcott K C et al (2016)Microscale screening of antibody libraries as maytansinoid antibody-drugconjugates, MAbs 8:513-23). In addition, similar methods to the abovecan be used to conjugate drugs and toxins to non-IgG formats withdisulfide bonds, such as Vh-Fcs.

Example 4. Demonstration of Enhanced Cytotoxicity of pH-Engineered ABPCADCs Specific for FOLR1 in FOLR1+ Cells as Compared to a Control ABPCADC Specific for FOLR1

The cytotoxic activity of both pH-engineered ADCs specific for FOLR1(e.g., a pH-engineered FOLR1-IgG-DC) and control ABPC ADCs specific forFOLR1 (e.g., a control ABPC FOLR1-IgG-DC) are separately evaluated on apanel of FOLR1+ cell lines expressing a variety of antigen densities(e.g., as described herein) and a FOLR1− cell line (e.g., A431),selected using the methods described herein, and, optionally, cellsexpressing transgenic FOLR1, e.g., HEK293 cells transfected with FOLR1using methods known in the art (e.g., Expi293™ Expression System KitThermoFisher Catalog number: A14635). For purposes of validation, priorto use, all cell lines are tested for expression of FOLR1 using methodsknown to the art, e.g., qPCR, flow cytometry, mRNA RPKM, and antibodystaining using anti-FOLR1 antibodies known to the art (e.g., asdescribed herein) followed by visualization of the stain usingfluorescence microscopy, immunohistochemistry, flow cytometry, ELISA, orother methods known to the art. To evaluate the cytotoxicity ofcompounds, cells are seeded at approximately 10-40,000 per well in 150microliters of culture medium, then treated with graded doses ofcompounds from 1 pM to 1 μM in quadruplicates at the initiation of theassay. Cytotoxicity assays are carried out for 96 hours after additionof test compounds. Fifty microliters of resazurin dye are added to eachwell during the last 4 to 6 hours of the incubation to assess viablecells at the end of culture. Dye reduction is determined by fluorescencespectrometry using the excitation and emission wavelengths of 535 nm and590 nm, respectively. For analysis, the extent of resazurin reduction bythe treated cells is compared to that of untreated control cells, andpercent cytotoxicity is determined. Alternatively, a WST-8 kit is usedto measure cytotoxicity per the manufacturer's instructions (e.g.,Dojindo Molecular Technologies Catalog #CCK-8). IC50, the concentrationat which half-maximal killing is observed, is calculated usingcurve-fitting methods known in the art. Upon analysis of the data, itcan be determined that pH-engineered and control ABPC ADCs specific forFOLR1 are substantially cytotoxic to one or more FOLR1+ cell line, butless toxic to FOLR1-cells. It also can be determined that pH-engineeredADCs specific for FOLR1 are more cytotoxic to one or more FOLR1+ celllines than control ABPC ADCs specific for FOLR1 because: a) they showgreater depth of killing at one or more concentrations or, b) they showlower IC50 or, c) they show a greater ratio of their dissociationconstant KD on cells at neutral pH (as described herein) divided bytheir IC50 on those same cells.

Additionally, the cytotoxic activity of ABPCs specific for FOLR1 can bemeasured in a secondary ADC assay. Secondary ADC assays are known in theart (e.g., Moradec Cat # αHFc-NC-MMAF and Cat #αHFc-CL-MMAE, andassociated manufacturer's instructions). Briefly, the assay is carriedout as in the previous paragraph, except the ABPC specific for FOLR1 issubstituted for the ADC specific for FOLR1, and to evaluate thecytotoxicity of compounds, cells are seeded at approximately 10-40,000per well in 150 microliters of culture medium, then treated with gradeddoses of ABPC specific for FOLR1 from 1 pM to 1 μM (final concentrationin culture medium, having been pre-mixed with 100 nM, finalconcentration in culture medium, of Moradec Cat #αHFc-NC-MMAF secondaryADC reagent and pre-incubated at 37° C. for 30 min before addition ofthe mixture to the culture medium) in quadruplicates at the initiationof the assay.

The cytotoxic activity of pH-engineered ADCs specific for FOLR1 andcontrol ABPC ADCs specific for FOLR1 conjugates, as well as ABPCsspecific for FOLR1 in a secondary ADC assay, are additionally measuredby a cell proliferation assay employing the following protocol (PromegaCorp. Technical Bulletin TB288; Mendoza et al., Cancer Res.62:5485-5488, 2002):

1. An aliquot of 100 microliters of cell culture containing about 104cells (e.g., FOLR1+ cells as described herein) in medium is deposited ineach well of a 96-well, opaque-walled plate.

2. Control wells are prepared containing medium and without cells.

3. ADC specific for FOLR1 is added to the experimental wells at a rangeof concentrations from 1 pM-1 uM and incubated for 1-5 days.Alternatively, in a secondary ADC assay, 100 nM secondary ADC reagent(final concentration in culture medium, Moradec Cat #αHFc-NC-MMAF) andABPC specific for FOLR1 at a range of concentrations from 1 pM-1 uM(final concentration in culture medium) are pre-mixed and pre-incubatedat 37° C. for 30 min before addition of the mixture to the culturemedium, and incubated for 1-5 days.

4. The plates are equilibrated to room temperature for approximately 30minutes.

5. A volume of CellTiter-Glo Reagent equal to the volume of cell culturemedium present in each well is added.

6. The contents are mixed for 2 minutes on an orbital shaker to inducecell lysis.

7. The plate is incubated at room temperature for 10 minutes tostabilize the luminescence signal.

8. Luminescence is recorded and reported in graphs as RLU=relativeluminescence units.

Example 5. Demonstration of Enhanced Toxin Liberation of pH-EngineeredABPC ADCs Specific for FOLR1 in FOLR1+ Cells as Compared to a ControlABPC ADC Specific for FOLR1

The pH-engineered ADCs specific for FOLR1 (e.g., a pH-engineeredFOLR1-IgG-DC) can also demonstrate increased toxin liberation in FOLR1+cells as compared to a control ABPC ADC specific for FOLR1 (e.g., acontrol ABPC FOLR1-IgG-DC). After treatment of FOLR1+ cells withpH-engineered and control ABPC ADCs specific for FOLR1 as describedherein, an LC-MS/MS method is used to quantify unconjugated (i.e.,liberated) MMAE in treated FOLR1+ cells (Singh, A. P. and Shah, D. K.Drug Metabolism and Disposition 45.11 (2017): 1120-1132.) An LC-MS/MSsystem with electrospray interphase and triple quadrupole massspectrometer is used. For the detection of MMAE, a XBridge BEH Amidecolumn (Waters, Milford, Mass.) is used with mobile phase A as water(with 5 mM ammonium formate and 0.1% formic acid) and mobile phase B as95:5 acetonitrile/water (with 0.1% formic acid and 1 mM ammoniumformate), using a gradient at a flow rate of 0.25 mL/min at 40° C. Thetotal duration of the chromatographic run is 12 minutes, where two MRMscans (718.5/686.5 and 718.5/152.1 amu) are monitored. Deuterated (d8)MMAE (MCE MedChem Express, Monmouth Junction, N.J.) is used as aninternal standard. First, an equation for quantifying unconjugated MMAEin a biological sample is derived by dividing the peak area for eachdrug standard by the peak area obtained for the internal standard. Theresultant peak area ratios are then plotted as a function of thestandard concentrations, and data points are fitted to the curve usinglinear regression. Three QC samples are included in the low, middle, andupper ranges of the standard curve to assess the predictive capabilityof the developed standard curve. The standard curves obtained are thenused to deduce the observed concentrations of MMAE in a biologic sample.For measurement of MMAE concentration, treated cell samples are pelletedand reconstituted in fresh media to a final concentration of 0.25million cells/100 μL. Samples are spiked with d8-MMAE (1 ng/mL) beforeperforming cell lysis by the addition of a 2-fold volume of ice-coldmethanol followed by freeze-thaw cycle of 45 minutes at −20° C. Thefinal cell lysate is obtained by centrifuging the samples at 13,000 rpmfor 15 minutes at 4° C. followed by collection of supernatant. For thepreparation of standards and QC samples, a fresh cell suspension (0.25million/100 μl) is spiked with known concentrations of MMAE and internalstandard (d8-MMAE) before a procedure similar to the cell lysismentioned above. The resulting cell lysates are then evaporated andreconstituted in mobile phase B before injection into LC-MS/MS. Theconcentration of unconjugated MMAE in lysates of FOLR1+ cells treatedwith pH-engineered ADCs specific for FOLR1 is observed to be greaterthan that in FOLR1+ cells treated with control ABPC ADC specific forFOLR1.

For tubulin-inhibiting toxins, toxin liberation is also assessed bymonitoring of cell viability and cell cycle phase. ˜2.0×10 {circumflexover ( )}5 FOLR1+ cells are plated in a 96-well flat bottom plate andtreated with pH-engineered and control ABPC ADCs specific for FOLR1 asdescribed herein. After treatment, cells are transferred to a 96-roundbottom plate, and the plate is centrifuged at 400 rcf for 2 min todecant supernatant. Decanted cells are stained with Live/Dead eFluor660. Cells are then centrifuged and washed with FACS buffer (PBS with 2%FBS), after which cell cycle distribution is analyzed with a BDCycletest™ Plus DNA Kit (cat #340242).

Briefly, cells are re-suspended in 76 ul Solution A and incubated for 10min at room temperature. 61 μL Solution B is then added, and cells areincubated for another 10 min at room temperature. Finally, 61 μL, ofcold Solution C is added, and cells are again incubated for 10 min atroom temp. Immediately after the last incubation step, cells areanalyzed by flow cytometry (without washing) at a flow rate of 10μL/sec. Increased G2/M-phase arrest can be observed with exposure topH-engineered ADCs specific for FOLR1 as compared to control ABPC ADCspecific for FOLR1.

For DNA-damaging toxins (e.g., pyrrolobenzodiazepine or “PBD”), DNAdamage is assessed by measuring the phosphorylated histone H2AX (γH2AX).H2AX is normally phosphorylated in response to double-strand breaks inDNA: however, increased levels γH2AX may also be observed as a result oftreatment with DNA-cross-linking toxins such as PBD or cisplatin (Huang,X. et al. 2004, Cytometry Part A 58A, 99-110). FOLR1+ cells are treatedwith pH-engineered and control ABPC ADCs specific for FOLR1 as describedherein. After treatment, cells are rinsed with PBS, and then fixed insuspension in 1% methanol-free formaldehyde (Polysciences, Warrington,Pa.) in PBS at 0° C. for 15 min. Cells are resuspended in 70% ethanolfor at least 2 h at −20° C. Cells are then washed twice in PBS andsuspended in 0.2% Triton X-100 (Sigma) in a 1% (w/v) solution of BSA(Sigma) in PBS for 30 min to suppress nonspecific Ab binding. Cells arecentrifuged again (200 g, 5 min) and the cell pellet is suspended in 100μL of 1% BSA containing 1:800 diluted anti-histone γH2AX polyclonal Ab(Trevigen, Gaithersburg, Md.). The cells are then incubated overnight at4° C., washed twice with PBS, and resuspended in 100 μl of 1:30 dilutedFITC-conjugated F(ab′)2 fragment of swine anti-rabbit immunoglobulin(DAKO, Carpinteria, Calif.) for 30 min at room temperature in the dark.The cells are then counterstained with 5 μg/mL of PI (Molecular Probes,Eugene, Oreg.) dissolved in PBS containing 100 μg/mL of DNase-free RNaseA (Sigma), for 20 min at room temperature. Cellular fluorescence of theFITC γH2AX signal and the PI counterstain are measured using flowcytometry using methods known in the art. When comparing cells withinthe same stage of the cell cycle (based on total DNA content), treatedFOLR1+ cells can be observed to have an increased FITC γH2AX signalrelative to untreated FOLR1+ cells (which serve as a baseline).Furthermore, FOLR1+ cells treated with pH-engineered ADCs specific forFOLR1 can be observed to have a greater increase in levels of γH2AX overbaseline than cells treated with a control ABPC ADC specific for FOLR1.In addition to the γH2AX assay, DNA cross-linking can be more directlyassessed with a Comet assay (Chandna, S. (2004) Cytometry 61A, 127-133).

In addition, as disclosed herein, pH-engineered and control ABPCs can beassayed using the methods in this example without direct conjugation byperforming a secondary ADC assay instead of using primary conjugatedADCs.

Example 6. Demonstration of Decreased Half-Life of pH-Engineered ABPCsSpecific for FOLR1 as Compared to a Control ABPC Specific for FOLR1

One of the surprising aspects of the pH-engineered ABPCs specific forFOLR1 described by the invention can be their ability to facilitateincreased dissociation of ABPCs from the FOLR1 within the endosome orlysosome resulting in a decreased serum half-life relative to controlABPCs specific for FOLR1 or ABPCs that are not specific for FOLR1. Thisdecreased serum half-life is due to the enhanced frequency with whichpH-engineered ABPCs specific for FOLR1 are cleared from circulation dueto their enhanced cellular internalization once bound to FOLR1, whichover time can be observed through a decrease in serum concentration ofunbound pH-engineered ABPC specific for FOLR1. To demonstrate theseproperties, a series of animal studies in mice and/or monkeys isperformed using pH-engineered ABPC specific for FOLR1 and control ABPCspecific for FOLR1 using methods known to the art (e.g., Gupta, P., etal. (2016), mAbs, 8:5, 991-997). Briefly, to conduct mouse studies, asingle intravenous bolus (e.g., 5 mg/kg) of either pH-engineered ABPCspecific for FOLR1 or control ABPC specific for FOLR1 is administeredvia tail vein to two groups of NOD SCID mice (e.g. Jackson LabsNOD.CB17-Prkdcscid/J Stock No: 001303) xenografted with a FOLR1+ cellline (e.g., as described herein). Xenografted mice are prepared bygrowing 1-5 million FOLR1+ cells in vitro and inoculating subcutaneouslyinto the right flank of the mouse. Tumors are size matched at 300 mm3.Measurements of the length (L) and width (W) of the tumors are taken viaelectronic caliper and the volume is calculated according to thefollowing equation: V=L×W{circumflex over ( )}2/2. Blood samples arecollected via retro-orbital bleeds from each group at each of thefollowing time points: 15 m, 30 m, 1 h, 8 h, 24 h, and 3 d, 7 d, 10 d,14 d, 17 d, 21 d, and 28 d. Samples are processed to collect serum, andantibody concentrations are quantified using ELISA or other methodsknown to the art (e.g., PAC assay or MAC assay; Fischer, S. K. et al.(2012), mAbs, 4:5, 623-631, utilizing, e.g., anti-human Fc antibodyJackson ImmunoResearch Labs, Cat #109-006-006). Antibody concentrationsof pH-engineered ABPC specific for FOLR1 and control ABPC specific forFOLR1 are plotted as a function of time. Upon analysis of the data, itcan be observed that the pH-engineered ABPC specific for FOLR1 has asignificantly shorter serum half-life relative to control ABPC specificfor FOLR1, thereby demonstrating the ability of the pH-engineered ABPCspecific for FOLR1's pH dependence to facilitate an enhanceddissociation within the endosome or lysosome relative to other, similarbinders (e.g., control ABPC specific for FOLR1) that bind the sameantigen but that differ in their pH dependence. If the pH-engineered andcontrol ABPCs specific for FOLR1 are cross-reactive with the mousehomolog of FOLR1, a similar experiment can be repeated withnon-xenografted mice.

Optionally, if the pH-engineered and control ABPCs specific for FOLR1are cross-reactive with the cynomolgus monkey homolog of FOLR1, asimilar experiment can be performed on monkeys (e.g., cynomolgusmonkeys). An equal number of male and female monkeys (e.g., n=1-2 each)are administered a bolus of either pH-engineered ABPC specific for FOLR1or control ABPC specific for FOLR1 at a dose of, e.g., 1 mg/kg viasaphenous vein injection. Alternatively, several different doses ofFOLR1-binding protein are administered across a group of severalmonkeys. Blood samples are collected via the peripheral vein or femoralvein at intervals similar to those described above, and analyzed for thepresence of either pH-engineered ABPC specific for FOLR1 or control ABPCspecific for FOLR1 using methods known to the art (e.g., ELISA). Uponanalysis of the data, it can be observed that pH-engineered ABPCspecific for FOLR1 has a significantly shorter serum half-life relativeto control ABPC specific for FOLR1, thereby demonstrating the ability ofpH-engineered ABPC specific for FOLR1 to facilitate an enhanceddissociation within the endosome or lysosome relative to other, similarbinders (e.g., control ABPC specific for FOLR1) that bind the sameantigen but that differ in their pH dependence. In some cases, thiseffect is observed only in certain doses, whereas in others it isobserved across doses.

In addition, the half life of pH-engineered and control ABPC ADCsspecific for FOLR1 can be assessed using the above methods bysubstituting pH-engineered and control ABPC ADCs specific for FOLR1 forthe pH-engineered and control ABPCs specific for FOLR1 (i.e., studyingthe ABPCs after conjugation to a drug or toxin, as described herein).

Example 7. Increased Potency of pH-Engineered ADCs Specific for FOLR1Vs. a Control ABPC ADC Specific for FOLR1 in Mouse Xenograft Models

The enhanced anti-tumor activity of the pH-engineered ADCs specific forFOLR1 against FOLR1+ tumors can be demonstrated in a subcutaneousxenograft model of FOLR1+ cells. For the experiments, 1-5 million FOLR1+cells are grown in vitro and inoculated subcutaneously per mouse intothe right flank of female immunodeficient (e.g., SCID-Beige or NOD scid)mice.

Tumors are size matched at 100-200 mm3, and dosed intraperitoneally (IP)(1 dose given every ˜4-7 days for a total of ˜2-6 doses). Measurementsof the length (L) and width (W) of the tumors are taken via electroniccaliper and the volume is calculated according to the followingequation: V=LXWA2/2. A bolus (e.g., 5 mg/kg) of either pH-engineered ADCspecific for FOLR1 or control ABPC ADC specific for FOLR1 isadministered via tail vein. Tumor growth inhibition (TGI) and tumorgrowth delay (TGD) and survival are significantly improved withadministration of pH-engineered ADC specific for FOLR1 compared toadministration of control ABPC ADC specific for FOLR1 at the sameregimen.

Optionally, spread of tumor cells into the various tissues is determinedin sacrificed animals. Metastasis is measured according to Schneider,T., et al., Clin. Exp. Metas. 19 (2002) 571-582. Briefly, tissues areharvested and human Alu sequences are quantified by real-time PCR.Higher human DNA levels, quantified by real-time PCR, correspond tohigher levels of metastasis. Levels of human Alu sequences (correlatingto invasion of tumor cells into secondary tissue) are significantlylower in animals treated with pH-engineered ADC specific for FOLR1,corresponding to reduced metastasis, compared to mice treated withcontrol ABPC ADC specific for FOLR1 at the same regimen. Alternatively,the enhanced anti-tumor activity of the pH-engineered ADC specific forFOLR1 can be shown in FOLR1+ patient-derived xenograft models (e.g.,available from Oncotest GmbH).

Example 8. Creation of a pH-Engineered Bispecific FOLR1 Bispecific ABPCand Demonstration of Exemplary Properties as Compared to a ControlBispecific ABPC

To create a pH-engineered ABPC specific for FOLR1 with modified toxicityand internalization properties, a bispecific antibody that binds twodifferent epitopes on FOLR1 is constructed. It is known in the art thatbiparatopic antibodies can show increased antigen-dependentinternalization, and are therefore useful for applications such asantibody-drug conjugates (e.g., see Li et al (2016) A BiparatopicHER2-Targeting Antibody-Drug Conjugate Induces Tumor Regression inPrimary Models Refractory to or Ineligible for HER2-Targeted Therapy,Cancer Cell 29:117-29). Briefly, a pH-engineered FOLR1×FOLR1 bispecific,biparatopic ABPC specific for FOLR1 is assembled using light chain/heavychain pairs from two different pH-engineered ABPCs specific for FOLR1,each of which binds a distinct epitope on FOLR1 that does not overlapwith the other epitope. A set of pH-engineered ABPCs specific for FOLR1that bind non-overlapping epitopes are discovered, e.g., using themethods described herein, or others known to one of ordinary skill inthe art. Briefly, two binders are selected on the basis that they bindsubstantially different epitopes on FOLR1, as determined by, e.g., abinding competition assay as in Abdiche Y N et al (2009) Exploringblocking assays using Octet, ProteOn, and Biacore biosensors, AnalBiochem 386:172-80. Alternatively, briefly, as described herein, cellculture supernatants of cells transfected with a first ABPC specific forFOLR1 are normalized to an antibody expression level of 50 μg/mL, andcaptured on an anti-human Fc sensor (Forte Bio). A baseline isestablished using 1× kinetics buffer (Forte Bio), and the sensor isassociated with 50 nM of FOLR1 in 1×PBS (that has been mixed andpre-incubated for 30 min at 37 degrees C. with a second ABPC specificfor FOLR1 transfection supernatant or the first ABPC specific for FOLR1transfection supernatant, both normalized to 50 ug/mL) at pH 7.4 for 300sec to generate an association curve. If the association rate in thepresence of the second ABPC specific for FOLR1 is significantly faster(as calculated by the instrument software, or as seen by an elevatedlevel of association over time) than the association rate in thepresence of the first ABPC specific for FOLR1, then the second ABPCspecific for FOLR1 is deemed to bind a non-overlapping epitope of FOLR1.Optionally, each antibody is screened for its internazation propertieswhen bound to its epitope on a cell expressing FOLR1, andwell-internalizing antibodies are selected. Assays for determining theinternalization rate of a molecule present on the surface of a cell areknown to the art. See, e.g., Wiley et al. (1991) J. Biol. Chem. 266:11083-11094; and Sorkin and Duex (2010) Curr. Protoc. Cell Biol.Chapter, Unit-15.14; Vainshtein et al. (2015) Pharm Res. 32: 286-299.Once selected, heavy and light chain constructs with engineeredmutations for heavy and light chain pairing (Spiess et al., “Alternativemolecular formats and therapeutic applications of bispecificantibodies,” 2015) are synthesized for both arms. Bispecific ABPCsspecific for FOLR1 are produced by co-expression of corresponding heavyand light chain plasmids in, e.g., Expi293 cells. Cell culturesupernatants are harvested and subjected to Protein A purification.Heterodimeric ABPCs specific for FOLR1 are separated from homodimericspecies via additional purification steps such as ion exchangechromatography, hydrophobic interaction chromatography, and mixed modechromatography.

The purified pH-engineered FOLR1×FOLR1 bispecific, biparatopic ABPCsspecific for FOLR1 are characterized via mass spectrometry to confirmthe purity and absence of homodimeric species and size exclusionchromatography to confirm the presence of monomeric antigen-bindingprotein construct species. For the product antibody, binding to theFOLR1 is confirmed via Biacore analysis. Other methods of bispecificantibody production are known to the art and could also be used tocreate a bispecific antibody, e.g., the FOLR1×FOLR1 bispecific,biparatopic ABPCs specific for FOLR1 described herein (e.g., Labrijn etal (2014) “Controlled Fab-arm exchange for the generation of stablebispecific IgG1” Nature Protcols 9:2450-2463, accessed athttp://www.nature.com/nprot/journal/v9/n10/abs/nprot.2014.169.html), aswould be apparent to one of ordinary skill in the art. Alternatively,instead of a FOLR1×FOLR1 ABPC specific for FOLR1, a pH-engineeredFOLR1×BINDER ABPC specific for FOLR1 can be constructed using similarmethods apparent to one skilled in the art, where BINDER is any antibodythat has been published in the art or discovered using methods likethose herein or those known in the art (e.g., display-based orimmunization-based methods).

Next, exemplary properties of pH-engineered FOLR1×FOLR1 ABPCs specificfor FOLR1 can be demonstrated using the methods described herein, withthe appropriate control being a control ABPC monospecific or bispecificABPC specific for FOLR1. Briefly, it can be shown that, as compared to acontrol, the pH-engineered FOLR1×FOLR1 ABPCs specific for FOLR1: a) bindin a pH-dependent manner to cells, e.g., bind at a neutral pH but not anacidic pH and b) release from cells in a pH-dependent manner, e.g. bindat a neutral pH and release at an acidic pH and c) show enhancedendolysosomal accumulation in FOLR1+ cells and d) show increased FOLR1antigen density after exposure to FOLR1+ cells and e) when conjugated toa toxin, show increased cytotoxicity to FOLR1+ cells and 0 whenconjugated to a toxin, show increased toxin liberation when incubatedwith FOLR1+ cells and g) show decreased half life when exposed to FOLR1antigen in a relevant animal model and h) when conjugated to a toxin,show increased efficacy in a mouse xenograft model of FOLR1+ cells.Similarly, the exemplary properties of pH-engineered FOLR1×BINDER ABPCsspecific for FOLR1 can be demonstrated using the methods describedherein, with the appropriate control being a control ABPC FOLR1×BINDERbispecific ABPC specific for FOLR1.

Example 9. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding (Altwerger G et al (2018) “In Vitro and In Vivo Activity ofIMGN853, an Antibody—Drug Conjugate Targeting Folate Receptor AlphaLinked to DM4, in Biologically Aggressive Endometrial Cancers” MolecularCancer Therapeutics 17(5): 1003-1011). We selected mirvetuximab (Heavychain SEQ ID NO: 1, Light chain SEQ ID NO: 2) as a FOLR1-bindingmonoclonal antibody for pH engineering via histidine scanning. Briefly,CDRs in the heavy chain were identified using the methods described byKabat et al (Kabat et al. (1992) Sequences of Proteins of ImmunologicalInterest, DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT uniquenumbering for Immunoglobulins, T cell receptors and Ig-like domains” TheImmunologist 7, 132-136), and for each CDR, residues falling undereither or both Kabat and IMGT CDR definitions were called as CDRresidues. To generate pH-dependent sequence variants, individual aminoacid residues within the heavy chain CDRs were systematicallysubstituted with a histidine, one at a time (MYT0597-MYT0637). In caseswhere the starting CDR residue was a histidine, it was mutated to analanine. Antibody variants with only one histidine or alanine mutationin a heavy chain CDR were generated by co-transfection of Expi293 cellswith a) one heavy chain sequence variant, and b) the correspondingstarting ABPC light chain using methods known to the art. After allowingfor four days of protein expression, cell culture supernatants werecollected, quantified by SDS-PAGE analysis, (FIG. 1), and the pHdependence of the variant was evaluated using biolayer interferometry(BLI) on an Octet RED 384 instrument. Briefly, 100 μL, of cell culturesupernatant was diluted into 1004, of 1× PBST pH 7.4 for loading ontothe sensor tips. Diluted supernatants were then captured on ananti-human Fc sensor (Forte Bio). A baseline was established using 1×PBST (50 mM Potassium Phosphate Buffer+150 mM NaCl+0.05% Tween 20) pH7.4, and the sensor was associated with 50 nM of FOLR1 (R&D Systems, Cat#5646-FR) in 1× PBST pH 7.4 for 120 sec to generate an associationcurve. In the dissociation phase, the antibody-antigen complex on thesensor was exposed to 1× PBST pH 7.4 for 300-600 sec. Baseline,association, and dissociation were repeated using 1× PBST pH 5.4throughout in a separate condition. Association and dissociation phasecurves were examined for the starting ABPC antibody (with nosubstitutions) and each corresponding antibody variant at pH 5.4 and pH7.4 to inform on two criteria: a) enhanced dissociation (e.g., higherkoff values) at pH 5.4 due to histidine or alanine substitution comparedto the starting ABPC (with no substitutions), and b) reduceddissociation at pH 7.4 (e.g., lower koff values) compared to pH 5.4 inthe antibody variant itself and with the starting ABPC (with nosubstitutions). Heavy chain variants that showed either enhanceddissociation at pH 5.4 or reduced dissociation at pH 7.4 or both (ascompared to the starting ABPC), as shown in FIG. 2 were selected forfurther analysis (e.g, MYT0598, MYT0601, MYT0603, MYT0605-MYT0608,MYT0610, MYT0612, MYT0614, MYT0615, MYT0617-MYT0620, MYT0627-MYT0630,MYT0632, MYT0633, MYT0635, and MYT0637). It was also noted that whilesome histidine and alanine mutations obliterated FOLR1 binding (e.g.,MYT0613, MYT0631, and MYT0634), others were tolerated with little (e.g.,less than 1-fold change in dissociation constant KD or dissociationrate) or no change in FOLR1 binding kinetics (e.g., MYT0597, MYT0599,MYT0600, MYT0602, MYT0604, MYT0611, MYT0616, MYT0621-MYT0626, andMYT0636). Especially because histidine is a large, positively chargedamino acid, these variants with no change were noted as positions in theheavy chain that may tolerate a wide range of mutations and lead toantibodies with different sequence but similar binding properties, adesignation that is not otherwise apparent.

Example 10. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding [Altwerger G et al (2018) “In Vitro and In Vivo Activity ofIMGN853, an Antibody—Drug Conjugate Targeting Folate Receptor AlphaLinked to DM4, in Biologically Aggressive Endometrial Cancers” MolecularCancer Therapeutics 17(5): 1003-1011]. We selected mirvetuximab (Heavychain SEQ ID NO: 1, Light chain SEQ ID NO: 2) as a FOLR1-bindingmonoclonal antibody for pH engineering via histidine scanning. Briefly,CDRs in the light chain were identified using the methods described byKabat et al (Kabat et al. (1992) Sequences of Proteins of ImmunologicalInterest, DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT uniquenumbering for Immunoglobulins, T cell receptors and Ig-like domains” TheImmunologist 7, 132-136), and for each CDR, residues falling undereither or both Kabat and IMGT CDR definitions were called as CDRresidues. To generate pH-dependent sequence variants, individual aminoacid residues within the light chain CDRs were systematicallysubstituted with a histidine, one at a time (MYT1559-MYT1589). In caseswhere the starting CDR residue was a histidine, it was mutated to analanine. Antibody variants with only one histidine or alanine mutationin a light chain CDR were generated by co-transfection of Expi293 cellswith a) one light chain sequence variant, and b) the correspondingstarting ABPC heavy chain using methods known to the art. After allowingfor four days of protein expression, cell culture supernatants werecollected, quantified by SDS-PAGE analysis (FIG. 4), and the pHdependence of the variant was evaluated using biolayer interferometry(BLI) on an Octet RED 384 instrument. Briefly, 254 of cell culturesupernatant was diluted into 1754 of 1× PBST pH 7.4 for loading onto thesensor tips. Diluted supernatants were then captured on an anti-human Fcsensor (Forte Bio). A baseline was established using 1× PBST (50 mMPotassium Phosphate Buffer+150 mM NaCl+0.05% Tween 20) pH 7.4, and thesensor was associated with 50 nM of FOLR1 (R&D Systems, Cat #5646-FR,Lot No. RTI0418011) in 1×PBST pH 7.4 for 120 sec to generate anassociation curve. In the dissociation phase, the antibody-antigencomplex on the sensor was exposed to 1× PBST pH 7.4 for 300-600 sec.Baseline, association, and dissociation were repeated using 1× PBST pH5.4 throughout in a separate condition. Association and dissociationphase curves were examined for the starting ABPC antibody (with nosubstitutions) and each corresponding antibody variant at pH 5.4 and pH7.4 to inform on two criteria: a) enhanced dissociation (e.g., higherkoff values) at pH 5.4 due to histidine or alanine substitution comparedto the starting ABPC (with no substitutions), and b) reduceddissociation at pH 7.4 (e.g., lower koff values) compared to pH 5.4 inthe antibody variant itself and with the starting ABPC (with nosubstitutions). Light chain variants that showed either enhanceddissociation at pH 5.4 or reduced dissociation at pH 7.4 or both (ascompared to the starting ABPC), as shown in FIG. 5 were selected forfurther analysis (e.g, MYT1563, MYT1565-MYT1567, MYT1569-MYT1571,MYT1573, MYT1575, MYT1579, MYT1581-MYT1586, and MYT1588)). It was alsonoted that some histidine and alanine mutations were tolerated withlittle (e.g., less than 1-fold change in dissociation constant KD ordissociation rate) or no change in FOLR1 binding kinetics (e.g.,MYT1559, MYT1561, MYT1562, MYT1568, MYT1574, MYT1576-MYT1578, MYT1580,and MYT1589). Especially because histidine is a large, positivelycharged amino acid, these variants with no change were noted aspositions in the light chain that may tolerate a wide range of mutationsand lead to antibodies with different sequence but similar bindingproperties, a designation that is not otherwise apparent.

Example 11. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding [Altwerger G et al (2018) “In Vitro and In Vivo Activity ofIMGN853, an Antibody—Drug Conjugate Targeting Folate Receptor AlphaLinked to DM4, in Biologically Aggressive Endometrial Cancers” MolecularCancer Therapeutics 17(5): 1003-1011]. We selected mirvetuximab (Heavychain SEQ ID NO: 1, Light chain SEQ ID NO: 2) as a FOLR1-bindingmonoclonal antibody for pH engineering via histidine scanning. Briefly,CDRs in the heavy chain were identified using the methods described byKabat et al (Kabat et al. (1992) Sequences of Proteins of ImmunologicalInterest, DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT uniquenumbering for Immunoglobulins, T cell receptors and Ig-like domains” TheImmunologist 7, 132-136), and for each CDR, residues falling undereither or both Kabat and IMGT CDR definitions were called as CDRresidues. To generate pH-dependent sequence variants, individual aminoacid mutations within the heavy chain CDRs that had been previouslyselected for further analysis in Example 9 were systematically combinedtwo or more at a time (MYT1142-MYT1161). In cases where the starting CDRresidue was a histidine, it was mutated to an alanine. Antibody variantswith two or more histidine or alanine mutations in the heavy chain CDRswere generated by co-transfection of Expi293 cells with a) one heavychain combinations sequence variant, and b) the corresponding startingABPC light chain using methods known to the art. After allowing for fourdays of protein expression, cell culture supernatants were collected,quantified by SDS-PAGE analysis (FIG. 7), and the pH dependence of thevariant was evaluated using biolayer interferometry (BLI) on an OctetRED 384 instrument. Briefly, 100 μL of cell culture supernatant wasdiluted into 1004 of 1× PBST pH 7.4 for loading onto the sensor tips.Diluted supernatants were then captured on an anti-human Fc sensor(Forte Bio). A baseline was established using 1× PBST (50 mM PotassiumPhosphate Buffer+150 mM NaCl+0.05% Tween 20) pH 7.4, and the sensor wasassociated with 50 nM of FOLR1 (R&D Systems, Cat #5646-FR, Lot No.RTI0418011) in 1×PBST pH 7.4 for 120 sec to generate an associationcurve. In the dissociation phase, the antibody-antigen complex on thesensor was exposed to 1× PBST pH 7.4 for 300-600 sec. Baseline,association, and dissociation were repeated using 1× PBST pH 5.4throughout in a separate condition. Association and dissociation phasecurves were examined for the starting ABPC antibody (with nosubstitutions) and each corresponding antibody variant at pH 5.4 and pH7.4 to inform on two criteria: a) enhanced dissociation (e.g., higherkoff values) at pH 5.4 due to histidine or alanine substitution comparedto the starting ABPC (with no substitutions), and b) reduceddissociation at pH 7.4 (e.g., lower koff values) compared to pH 5.4 inthe antibody variant itself and with the starting ABPC (with nosubstitutions). Heavy chain combinations variants that showed eitherenhanced dissociation at pH 5.4 or reduced dissociation at pH 7.4 orboth (as compared to the starting ABPC), as shown in FIG. 8 wereselected for further analysis (e.g, MYT1142-MYT1160).

Example 12. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding (Abrahams, Cristina et al. Preclinical Activity and Safety ofSTRO-002, a Novel ADC Targeting Folate Receptor Alpha for OvarianCancer. Poster session presented at: 12th Biennial Ovarian CancerResearch Symposium; 2018 Sep. 13-15. Seattle, Wash.). We selectedSTRO-002 (Heavy chain SEQ ID NO: 105, Light chain SEQ ID NO: 106) as aFOLR1-binding monoclonal antibody for pH engineering via histidinescanning. Briefly, CDRs in the heavy chain were identified using themethods described by Kabat et al (Kabat et al. (1992) Sequences ofProteins of Immunological Interest, DIANE publishing) and IMGT (LefrancMP (1999) “The IMGT unique numbering for Immunoglobulins, T cellreceptors and Ig-like domains” The Immunologist 7, 132-136), and foreach CDR, residues falling under either or both Kabat and IMGT CDRdefinitions were called as CDR residues. To generate pH-dependentsequence variants, individual amino acid residues within the heavy chainCDRs were systematically substituted with a histidine, one at a time(MYT2225-MYT2268). In cases where the starting CDR residue was ahistidine, it was mutated to an alanine. Antibody variants with only onehistidine or alanine mutation in a heavy chain CDR were generated byco-transfection of Expi293 cells with a) one heavy chain sequencevariant, and b) the corresponding starting ABPC light chain usingmethods known to the art. After allowing for four days of proteinexpression, cell culture supernatants were collected, quantified bySDS-PAGE analysis, (FIG. 10), and the pH dependence of the variant wasevaluated using biolayer interferometry (BLI) on an Octet RED 96einstrument. Briefly, 5 μL of cell culture supernatant was diluted into1954 of 1× PBST pH 7.4 for loading onto the sensor tips. Dilutedsupernatants were then captured on an anti-human Fc sensor (Forte Bio).A baseline was established using 1× PBST (50 mM Potassium PhosphateBuffer+150 mM NaCl+0.05% Tween 20) pH 7.4, and the sensor was associatedwith 50 nM of FOLR1 (R&D Systems, Cat #5646-FR, Lot No. RTI0419021) in1×PBST pH 7.4 for 120 sec to generate an association curve. In thedissociation phase, the antibody-antigen complex on the sensor wasexposed to 1× PBST pH 7.4 for 300-600 sec. Baseline, association, anddissociation were repeated using 1× PBST pH 5.4 throughout in a separatecondition. Association and dissociation phase curves were examined forthe starting ABPC antibody (with no substitutions) and eachcorresponding antibody variant at pH 5.4 and pH 7.4 to inform on twocriteria: a) enhanced dissociation (e.g., higher koff values) at pH 5.4due to histidine or alanine substitution compared to the starting ABPC(with no substitutions), and b) reduced dissociation at pH 7.4 (e.g.,lower koff values) compared to pH 5.4 in the antibody variant itself andwith the starting ABPC (with no substitutions). Heavy chain variantsthat showed either enhanced dissociation at pH 5.4 or reduceddissociation at pH 7.4 or both (as compared to the starting ABPC), asshown in FIG. 11 were selected for further analysis (e.g, MYT2228,MYT2232-MYT2238, MYT2240-MYT2242, MYT2256-MYT2258, and MYT2263-MYT2268).It was also noted that while some histidine and alanine mutationsobliterated FOLR1 binding (e.g., MYT2244, MYT2252, MYT2254, MYT2259, andMYT2261), others were tolerated with little (e.g., less than 1-foldchange in dissociation constant KD or dissociation rate) or no change inFOLR1 binding kinetics (e.g., MYT2225-MYT2227, MYT2229-MYT2231, MYT2239,MYT2243, MYT2245-MYT2251, MYT2253, MYT2255, MYT2260, and MYT2262).Especially because histidine is a large, positively charged amino acid,these variants with no change were noted as positions in the heavy chainthat may tolerate a wide range of mutations and lead to antibodies withdifferent sequence but similar binding properties, a designation that isnot otherwise apparent.

Example 13. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding (Abrahams, Cristina et al. Preclinical Activity and Safety ofSTRO-002, a Novel ADC Targeting Folate Receptor Alpha for OvarianCancer. Poster session presented at: 12th Biennial Ovarian CancerResearch Symposium; 2018 Sep. 13-15. Seattle, Wash.). We selectedSTRO-002 (Heavy chain SEQ ID NO: 105, Light chain SEQ ID NO: 106) as aFOLR1-binding monoclonal antibody for pH engineering via histidinescanning. Briefly, CDRs in the light chain were identified using themethods described by Kabat et al (Kabat et al. (1992) Sequences ofProteins of Immunological Interest, DIANE publishing) and IMGT (LefrancMP (1999) “The IMGT unique numbering for Immunoglobulins, T cellreceptors and Ig-like domains” The Immunologist 7, 132-136), and foreach CDR, residues falling under either or both Kabat and IMGT CDRdefinitions were called as CDR residues. To generate pH-dependentsequence variants, individual amino acid residues within the light chainCDRs were systematically substituted with a histidine, one at a time(MYT4493-MYT4519). In cases where the starting CDR residue was ahistidine, it was mutated to an alanine. Antibody variants with only onehistidine or alanine mutation in a light chain CDR were generated byco-transfection of Expi293 cells with a) one light chain sequencevariant, and b) the corresponding starting ABPC heavy chain usingmethods known to the art. After allowing for four days of proteinexpression, cell culture supernatants were collected, quantified bySDS-PAGE analysis (FIG. 13), and the pH dependence of the variant wasevaluated using biolayer interferometry (BLI) on an Octet RED 384instrument. Briefly, cell culture supernatants were diluted based onqualitative expression level of the variant determined by visualexamination of SDS-PAGE gels, 5 μL of cell culture supernatant wasdiluted into 195 μL of 1× PBST, pH 7.4 for high expressors and 100 μL ofcell culture supernatant was diluted into 100 μL of 1× PBST, pH 7.4 forlow expressors for loading onto the sensor tips. Diluted supernatantswere then captured on an anti-human Fc sensor (Forte Bio). A baselinewas established using 1× PBST (50 mM Potassium Phosphate Buffer+150 mMNaCl+0.05% Tween 20) pH 7.4, and the sensor was associated with 50 nM ofFOLR1 (R&D Systems, Cat #5646-FR, Lot No. RTI0419021) in 1×PBST pH 7.4for 120 sec to generate an association curve. In the dissociation phase,the antibody-antigen complex on the sensor was exposed to 1× PBST pH 7.4for 300-600 sec. Baseline, association, and dissociation were repeatedusing 1× PBST pH 5.4 throughout in a separate condition. Association anddissociation phase curves were examined for the starting ABPC antibody(with no substitutions) and each corresponding antibody variant at pH5.4 and pH 7.4 to inform on two criteria: a) enhanced dissociation(e.g., higher koff values) at pH 5.4 due to histidine or alaninesubstitution compared to the starting ABPC (with no substitutions), andb) reduced dissociation at pH 7.4 (e.g., lower koff values) compared topH 5.4 in the antibody variant itself and with the starting ABPC (withno substitutions). Light chain variants that showed either enhanceddissociation at pH 5.4 or reduced dissociation at pH 7.4 or both (ascompared to the starting ABPC), as shown in FIG. 14 were selected forfurther analysis (e.g, MYT4497-MYT4500, MYT4504, and MYT4513-MYT4518).It was also noted that while some histidine and alanine mutationsobliterated FOLR1 binding (e.g., MYT4501 and MYT4503), others weretolerated with little (e.g., less than 1-fold change in dissociationconstant KD or dissociation rate) or no change in FOLR1 binding kinetics(e.g., MYT4493-MYT4496, MYT4502, MYT4506-MYT4512, and MYT4519).Especially because histidine is a large, positively charged amino acid,these variants with no change were noted as positions in the light chainthat may tolerate a wide range of mutations and lead to antibodies withdifferent sequence but similar binding properties, a designation that isnot otherwise apparent.

Example 14. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding (Ebel W, Routhier E L, Foley B, et al. Preclinical evaluation ofMORAb-003, a humanized monoclonal antibody antagonizing folatereceptor-alpha. Cancer Immun. 2007; 7). We selected Farletuzumab (Heavychain SEQ ID NO: 184, Light chain SEQ ID NO: 185) as a FOLR1-bindingmonoclonal antibody for pH engineering via histidine scanning. Briefly,CDRs in the heavy chain were identified using the methods described byKabat et al (Kabat et al. (1992) Sequences of Proteins of ImmunologicalInterest, DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT uniquenumbering for Immunoglobulins, T cell receptors and Ig-like domains” TheImmunologist 7, 132-136), and for each CDR, residues falling undereither or both Kabat and IMGT CDR definitions were called as CDRresidues. To generate pH-dependent sequence variants, individual aminoacid residues within the heavy chain CDRs were systematicallysubstituted with a histidine, one at a time (MYT2185-MYT2223). In caseswhere the starting CDR residue was a histidine, it was mutated to analanine. Antibody variants with only one histidine or alanine mutationin a heavy chain CDR were generated by co-transfection of Expi293 cellswith a) one heavy chain sequence variant, and b) the correspondingstarting ABPC light chain using methods known to the art. After allowingfor four days of protein expression, cell culture supernatants werecollected, quantified by SDS-PAGE analysis, (FIG. 16), and the pHdependence of the variant was evaluated using biolayer interferometry(BLI) on an Octet RED 96e instrument. Briefly, cell culture supernatantswere diluted based on qualitative expression level of the variantdetermined by visual examination of SDS-PAGE gels, 5 μL of cell culturesupernatant was diluted into 195 μL of 1× PBST, pH 7.4 for highexpressors, 25 μL of cell culture supernatant was diluted into 175 μL of1× PBST, pH 7.4 for medium expressors and 100 μL of cell culturesupernatant was diluted into 100 μL of 1× PBST, pH 7.4 for lowexpressors for loading onto the sensor tips. Diluted supernatants werethen captured on an anti-human Fc sensor (Forte Bio). A baseline wasestablished using 1× PBST (50 mM Potassium Phosphate Buffer+150 mMNaCl+0.05% Tween 20) pH 7.4, and the sensor was associated with 50 nM ofFOLR1 (R&D Systems, Cat #5646-FR, Lot No. RT10419021) in 1× PBST pH 7.4for 120 sec to generate an association curve. In the dissociation phase,the antibody-antigen complex on the sensor was exposed to 1× PBST pH 7.4for 300-600 sec. Baseline, association, and dissociation were repeatedusing 1× PBST pH 5.4 throughout in a separate condition. Association anddissociation phase curves were examined for the starting ABPC antibody(with no substitutions) and each corresponding antibody variant at pH5.4 and pH 7.4 to inform on two criteria: a) enhanced dissociation(e.g., higher koff values) at pH 5.4 due to histidine or alaninesubstitution compared to the starting ABPC (with no substitutions), andb) reduced dissociation at pH 7.4 (e.g., lower koff values) compared topH 5.4 in the antibody variant itself and with the starting ABPC (withno substitutions). Heavy chain variants that showed either enhanceddissociation at pH 5.4 or reduced dissociation at pH 7.4 or both (ascompared to the starting ABPC), as shown in FIG. 17 were selected forfurther analysis (e.g, MYT2185-MYT2189, MYT2191-MYT2193, MYT2198,MYT2201, MYT2202, MYT2204, MYT2207, MYT2208, MYT2214, MYT2218, andMYT2220). It was also noted that while some histidine and alaninemutations obliterated FOLR1 binding (e.g., MYT2194-MYT2196, MYT2215,MYT2217, MYT2219, and MYT2221), others were tolerated with little (e.g.,less than 1-fold change in dissociation constant KD or dissociationrate) or no change in FOLR1 binding kinetics (e.g., MYT2190, MYT2199,MYT2203, MYT2205, MYT2206, MYT2209-MYT2211, MYT2216, MYT2222, andMYT2223). Especially because histidine is a large, positively chargedamino acid, these variants with no change were noted as positions in theheavy chain that may tolerate a wide range of mutations and lead toantibodies with different sequence but similar binding properties, adesignation that is not otherwise apparent.

Example 15. Construction and Screening of pH-Engineered FOLR1 ABPCs

Multiple FOLR1-binding monoclonal antibodies have been described in theliterature and can be used as a template for engineering pH-dependentbinding (Ebel W, Routhier E L, Foley B, et al. Preclinical evaluation ofMORAb-003, a humanized monoclonal antibody antagonizing folatereceptor-alpha. Cancer Immun. 2007; 7). We selected Farletuzumab (Heavychain SEQ ID NO: 184, Light chain SEQ ID NO: 185) as a FOLR1-bindingmonoclonal antibody for pH engineering via histidine scanning. Briefly,CDRs in the light chain were identified using the methods described byKabat et al (Kabat et al. (1992) Sequences of Proteins of ImmunologicalInterest, DIANE publishing) and IMGT (Lefranc MP (1999) “The IMGT uniquenumbering for Immunoglobulins, T cell receptors and Ig-like domains” TheImmunologist 7, 132-136), and for each CDR, residues falling undereither or both Kabat and IMGT CDR definitions were called as CDRresidues. To generate pH-dependent sequence variants, individual aminoacid residues within the light chain CDRs were systematicallysubstituted with a histidine, one at a time (MYT4520-MYT4546). In caseswhere the starting CDR residue was a histidine, it was mutated to analanine. Antibody variants with only one histidine or alanine mutationin a light chain CDR were generated by co-transfection of Expi293 cellswith a) one light chain sequence variant, and b) the correspondingstarting ABPC heavy chain using methods known to the art. After allowingfor four days of protein expression, cell culture supernatants werecollected, quantified by SDS-PAGE analysis (FIG. 19), and the pHdependence of the variant was evaluated using biolayer interferometry(BLI) on an Octet RED 96e instrument. Briefly, cell culture supernatantswere diluted based on qualitative expression level of the variantdetermined by visual examination of SDS-PAGE gels, 5 μL of cell culturesupernatant was diluted into 195 μL of 1× PBST, pH 7.4 for highexpressors, 25 μL of cell culture supernatant was diluted into 175 μL of1× PBST, pH 7.4 for medium expressors and 100 μL of cell culturesupernatant was diluted into 100 μL of 1× PBST, pH 7.4 for lowexpressors for loading onto the sensor tips. Diluted supernatants werethen captured on an anti-human Fc sensor (Forte Bio). A baseline wasestablished using 1× PBST (50 mM Potassium Phosphate Buffer+150 mMNaCl+0.05% Tween 20) pH 7.4, and the sensor was associated with 50 nM ofFOLR1 (R&D Systems, Cat #5646-FR, Lot No. RTI0419021) in 1× PBST pH 7.4for 120 sec to generate an association curve. In the dissociation phase,the antibody-antigen complex on the sensor was exposed to 1× PBST pH 7.4for 300-600 sec. Baseline, association, and dissociation were repeatedusing 1× PBST pH 5.4 throughout in a separate condition. Association anddissociation phase curves were examined for the starting ABPC antibody(with no substitutions) and each corresponding antibody variant at pH5.4 and pH 7.4 to inform on two criteria: a) enhanced dissociation(e.g., higher koff values) at pH 5.4 due to histidine or alaninesubstitution compared to the starting ABPC (with no substitutions), andb) reduced dissociation at pH 7.4 (e.g., lower koff values) compared topH 5.4 in the antibody variant itself and with the starting ABPC (withno substitutions). Light chain variants that showed either enhanceddissociation at pH 5.4 or reduced dissociation at pH 7.4 or both (ascompared to the starting ABPC), as shown in FIG. 20 were selected forfurther analysis (e.g, MYT4522, MYT4526-MYT4533, MYT4536, MYT4538,MYT4540, and MYT4542-MYT4546). It was also noted that some histidine andalanine mutations were tolerated with little (e.g., less than 1-foldchange in dissociation constant KD or dissociation rate) or no change inFOLR1 binding kinetics (e.g., MYT4520, MYT4521, MYT4523, MYT4524,MYT4534, MYT4535, MYT4537, MYT4539, and MYT4541). Especially becausehistidine is a large, positively charged amino acid, these variants withno change were noted as positions in the light chain that may tolerate awide range of mutations and lead to antibodies with different sequencebut similar binding properties, a designation that is not otherwiseapparent.

Example 16. Characterization of Cellular Internalization andEndolysosomal Delivery of pH Engineered Anti-FOLR1 ABPCs

Selected anti-FOLR1 pH engineered antibody variants from Examples 9 and11 were analyzed for internalization and endolysosomal delivery inNIH:OVCAR-3 (FOLR1+) cells. NIH:OVCAR-3 cells (ATCC; HTB-161) werecollected and resuspended in RPMI-1640 medium (ATCC; 30-2001)+20%GenClone heat inactivated fetal bovine serum (HI FBS) (GeneseeScientific; 25-514H). Cell counts were determined using trypan bluestaining and the Countess II FL Automated Cell Counter (Thermofisher;AMQAF1000). Cells were then diluted to 2,000,000 cells/mL and 50 μl/wellwas seeded into 96-well flat bottom cell culture plates (GeneseeScientific; 25-109). Anti-FOLR1 pH engineered antibody variants,starting ABPC antibodies, control IgG1 isotype control (BP0297,Bioxcell), and vehicle control were diluted in native culture media to100 nM and then mixed 1:1 with 300 nM Zenon pHrodo iFL Human IgGLabeling Reagent (ThermoFisher; Z25611). The mixture was incubated for20 minutes at room temperature, followed by addition of 50 μL to cells.The mixture of cells, anti-FOLR1 antibody variants, and Zenon pHrodo iFLHuman IgG Labeling Reagent was incubated at 37° C., 5% CO2 for 1-24hours. Following incubation, 100 μL of ice cold Flow Cytometry (FC)buffer (phosphate buffered saline (PBS), pH 7.4+2 mMethylenediaminetetraacetic acid (EDTA)+2% (v/v) HI FBS is added to eachwell. Cells were then spun down at 4° C. for 2 min at 2000 rpm, washedwith 200 μL ice cold FC buffer and resuspended in 100 μL ice cold FCbuffer. Mean green fluorescence intensity was detected using a BD AccuriC6 flow cytometer. Data was analyzed using Flowjo analysis software.pHrodo green is a pH sensitive dye that fluoresces in the low pHenvironment of the endosomes and lysosomes and therefore can be used toquantify antibody internalization and endolysosomal delivery.Internalization and endolysosomal delivery of anti-FOLR1 starting ABPCantibody mirvetuximab and variants in NIH:OVCAR-3 (FOLR1+) cells isshown in FIG. 22 as measured by pHrodo green mean fluorescenceintensity. Several pH engineered anti-FOLR1 antibody variants showedincreased mean fluorescence intensity relative to their correspondingstarting ABPC antibodies demonstrating that increased dissociation atlower pH leads to enhanced internalization and endolysosomal deliveryinside cells as shown by increased fluorescence or increasedfluorescence as compared to IgG1 isotype control. Increasedendolysosomal delivery is quantitated for each pH engineered anti-FOLR1antibody variant on the top of each bar as a ratio of: the variant'smean fluorescence intensity minus the mean fluorescence intensity of theIgG control, then all divided by the variant's corresponding startingABPC's mean fluorescence intensity minus the mean fluorescence intensityof the IgG control. For example MYT0603, MYT1150, and MYT1154, antibodyvariants of mirvetuximab, show increased internalization andendolysosomal delivery relative to mirvetuximab (MYT0596). Such pHengineered anti-FOLR1 antibody variants with increased mean fluorescenceintensity relative to their starting ABPC antibodies were selected forfurther analysis (MYT0603, MYT1150, and MYT1154).

Example 17. Characterization of Binding Affinity for Anti-FOLR1 mAbs

Binding affinity of selected anti-FOLR1 pH engineered antibody variantsfrom Examples 9 and 11 were measured on NIH:OVCAR-3 cells. 100,000 cellsper well were resuspended in 900 FC buffer in a 96 well deep well plate.Mirvetuximab and pH engineered antibody variants were serially dilutedat a 1:3 dilution. 1004 of diluted antibody was added to each well withfinal concentration ranging from ˜100 nM to 0.024 pM and incubated for 2hours at 4° C. Post incubation, the cells were spun at 2000 rpm for 2min and supernatant was discarded. Cells were washed twice with 500 μLof ice-cold FC buffer and resuspended with 100 μL of FC buffer. Thecells were then transferred from the deep well plate to 96 well roundbottom plate, spun at 2000 rpm for 2 min and incubated with 100 μL of 10μg/mL Alexa Fluor 488 conjugated goat anti-human IgG secondary antibody(ThermoFisher Scientific, A11013) for 30 min. Post incubation, cellswere washed with FC buffer and resuspended in 100 μL, of FC buffer toread on a BD Accuri C6 flow cytometer. Mean fluorescence intensity ateach concentration per sample was background subtracted and plotted asshown in FIG. 23. Binding affinity was measured as a dissociationconstant KD by GraphPad Prism assuming Michaelis-Menten bindingkinetics. MYT0603 and MYT1154 show high affinity binding to cell surfaceFOLR1 on NIH:OVCAR-3 cells in the pM-nM range confirming that variantscreated through pH engineering can retain functionally appropriateaffinities as compared to their corresponding starting ABPCs (e.g.,mirvetuximab). Variants with dissociation constants KD less than 100 nMwere selected for further analysis.

Example 18. Thermal Stability of Anti-FOLR1 mAbs

Protein melting temperature (Tm) was measured through the use ofDifferential Scanning Flourimetry (DSF). DSF visualizes proteinunfolding by measuring the fluorescent signal from the molecule SyproOrange (Thermo Scientific cat. no. S6650) as a protein unfolds due toheating. As a protein unfolds it exposes more hydrophilic regions to theSypro Orange dye, which in turns binds to these hydrophilic regionsresulting in increase in signal. The Tm for a protein is calculated asthe half-maximal of the unfolding transition and can be visualized byplotting the first derivative of the Sypro Orange signal and finding alocal maximum of this derivative plot. 20 μL of protein samples in 1×PBS, pH 7.4, was mixed with 5 μL of 25× Sypro Orange master mix,yielding a final concentration of 5× Sypro Orange. The samples wereadded to 96-well PCR plates (Thermo Scientific Cat. No. AB-2400/W) andsealed with optical covers (Thermo Scientific Cat. No. 4360954). The PCRplate was inserted into a real-time PCR machine (Thermo Scientific QuantStudio 3) and the plate temperature was stabilized for 3 minutes at 25°C. before ramping to 95° C. by 0.2° C. increments, stabilizing for 1second before the Sypro Orange signal was measured. The meltingtemperature (Tm) values for anti-FOLR1 variants are shown in FIG. 24.Several variants (MYT0614, MYT0619 and MYT1150) show similar meltingtemperature values to mirvetuximab confirming that variants createdthrough pH engineering can retain functionally appropriate thermalstabilities as compared to their corresponding starting ABPCs (e.g.,mirvetuximab). Variants (MYT0598, MYT0601, MYT0603, MYT0614, MYT0618,MYT0619, MYT1143, MYT1145, MYT1148, MYT1150, and MYT1154) with meltingtemperatures greater than or equal to the melting temperature of theircorresponding starting ABPC (e.g., mirvetuximab) minus 10° C. wereselected for further analysis.

The discoveries herein are in contrast to similar engineering on otherantigens such as CLEC12a and two other targets wherein multiple variantsper target showed enhanced dissociation at low pH, however, despite thefavorable pH-dependent binding properties of these variants (whichspecifically bound CLEC12a and the two other targets), they had lessthan 10% increase in cell internalization and endolysosomal delivery ascompared to the corresponding starting ABPC (e.g., the startingantibody). These variants (which specifically bound CLEC12a and the twoother targets) also had similar biophysical characteristics (e.g.,antibody expression, thermal stability, affinity at pH 7.4 etc.) to thecorresponding starting ABPC (e.g., the starting antibody) confirmingthat this was not specific to the biophysical properties of the testedvariant (i.e. the biophysical properties unrelated to enhanceddissociation at pH 5.4).

Exemplary Embodiments

Embodiment 1 is a pharmaceutical composition comprising an effectiveamount of an antigen-binding protein construct (ABPC) comprising: afirst antigen-binding domain that is capable of specifically bindingFOLR1 or an epitope of FOLR1 presented on the surface of a targetmammalian cell, wherein: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; or (b) thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0.

Embodiment 2 is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises a heavy chain variable domainof mirvetuximab with one or more amino acids substituted with ahistidine.

Embodiment is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises a light chain variable domainof mirvetuximab with one or more amino acids substituted with ahistidine.

Embodiment 4 is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises: a heavy chain variabledomain of mirvetuximab with one or more amino acids substituted with ahistidine; and a light chain variable domain of mirvetuximab with one ormore amino acids substituted with a histidine.

Embodiment 5 is the pharmaceutical composition of embodiment 2 or 4,wherein the heavy chain variable domain of mirvetuximab comprises SEQ IDNO: 1.

Embodiment 6 is the pharmaceutical composition of embodiment 3 or 4,wherein the light chain variable domain of mirvetuximab comprises SEQ IDNO: 2.

Embodiment 7 is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 3-5 substituted with a histidine.

Embodiment 8 the pharmaceutical composition of embodiment 1, wherein thefirst FOLR1-binding domain comprises a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 6-8 substituted with a histidine.

Embodiment 9 the pharmaceutical composition of embodiment 1, wherein thefirst FOLR1-binding domain comprises: a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 3-5 substituted with a histidine; and a light chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 6-8 substituted with a histidine.

Embodiment 10 is the pharmaceutical composition of embodiment 1, 2, or7, wherein the first antigen-binding domain comprises a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29, 31, 32, 33, 34, 35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103,104, 105, and 107.

Embodiment 11 is the pharmaceutical composition of embodiment 1, 3, or8, wherein the first antigen-binding domain comprises a light chainvariable domain that is at least 90% identical to SEQ ID NO: 2, whereinthe light chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 2 selected from the group consisting of: 28, 30,31, 32, 34, 35, 36, 55, 93, 94, 95, 96, 97, 98, and 100.

Embodiment 12 is the pharmaceutical composition of embodiment 1, 2, or7, wherein the first antigen-binding domain comprises a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at two or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,54, 58, and 59.

Embodiment 13 is the pharmaceutical composition of embodiment 1, 4, or9, wherein the first antigen-binding domain comprises: a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29; 31, 32, 33, 34, 35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103,104, 105, and 107; and a light chain variable domain that is at least90% identical to SEQ ID NO: 2, wherein the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 2 selectedfrom the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 93, 94,95, 96, 97, 98, and 100.

Embodiment 14 is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises a heavy chain variable domainof SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ IDNO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34,SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO:48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, or SEQ ID NO: 53.

Embodiment 15 is the pharmaceutical composition of embodiment 1 or 14,wherein the first antigen-binding domain comprises a light chainvariable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ IDNO: 61. SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQID NO: 68, SEQ ID NO: 70, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78,SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 16 is the pharmaceutical composition of embodiment 1, whereinthe first antigen-binding domain comprises a heavy chain variable domainSEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO:89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ IDNO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO:103.

Embodiment 17 is the pharmaceutical composition of embodiment 16,wherein the first antigen-binding domain comprises a light chainvariable domain of SEQ ID NO: 2; SEQ ID NO: 58, SEQ ID NO: 60, SEQ IDNO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQID NO: 68, SEQ ID NO: 70, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78,SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 18 is the pharmaceutical composition of any one ofembodiments 1-17, wherein the ABPC is degraded in the target mammaliancell following internalization of the ABPC by the target mammalian cell.

Embodiment 19 is the pharmaceutical composition of any one ofembodiments 1-18, wherein the ABPC further comprises a conjugated toxin,radioisotope, drug, or small molecule.

Embodiment 20 is the pharmaceutical composition of embodiment 19,wherein the composition provides for an increase in toxin liberation inthe target mammalian cell as compared to a composition comprising thesame amount of a control ABPC.

Embodiment 21 is the pharmaceutical composition of embodiment 20,wherein the composition provides for at least a 20% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 22 is the pharmaceutical composition of embodiment 21,wherein the composition provides for at least a 50% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 23 is the pharmaceutical composition of embodiment 20,wherein the composition provides for at least a 2-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 24 is the pharmaceutical composition of embodiment 23,wherein the composition provides for at least a 5-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 25 the pharmaceutical composition of any one of embodiments19-24, wherein the composition provides for an increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 26 is the pharmaceutical composition of embodiment 25,wherein the composition provides for at least a 20% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 27 is the pharmaceutical composition of embodiment 26,wherein the composition provides for at least a 50% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 28 is the pharmaceutical composition of embodiment 25,wherein the composition provides for at least a 2-fold increase intarget mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC.

Embodiment 29 is the pharmaceutical composition of embodiment 28,wherein the composition provides for at least a 5-fold increase intarget mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC.

Embodiment 30 is the pharmaceutical composition of any one ofembodiments 1-29, wherein the composition provides for an increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 31 is the pharmaceutical composition of embodiment 30,wherein the composition provides for at least a 20% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 32 is the pharmaceutical composition of embodiment 31,wherein the composition provides for at least a 50% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 33 is the pharmaceutical composition of embodiment 30,wherein the composition provides for at least a 2-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 34 is the pharmaceutical composition of embodiment 33,wherein the composition provides for at least a 5-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 35 is the pharmaceutical composition of any one ofembodiments 1-34, wherein the composition results in a less of areduction in the level of FOLR1 presented on the surface of the targetmammalian cell as compared to a composition comprising the same amountof a control ABPC.

Embodiment 36 is the pharmaceutical composition of any one ofembodiments 1-34, wherein the composition does not result in adetectable reduction in the level of the FOLR1 presented on the surfaceof the target mammalian cell.

Embodiment 37 a pharmaceutical composition comprising an effectiveamount of an antigen-binding protein construct (ABPC) comprising: afirst antigen-binding domain that is capable of specifically bindingFOLR1 or an epitope of FOLR1 presented on the surface of a targetmammalian cell; and a conjugated toxin, radioisotope, drug, or smallmolecule, wherein: (a) the dissociation rate of the firstantigen-binding domain at a pH of about 4.0 to about 6.5 is faster thanthe dissociation rate at a pH of about 7.0 to about 8.0; or thedissociation constant (KD) of the first antigen-binding domain at a pHof about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 toabout 8.0; and (b) the composition provides for one or more of: anincrease in toxin liberation in the target mammalian cell as compared toa composition comprising the same amount of a control ABPC; an increasein target mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC; and an increase in endolysosomaldelivery in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 38 is the pharmaceutical composition of embodiment 37,wherein the first antigen-binding domain comprises a heavy chainvariable domain of mirvetuximab with one or more amino acids substitutedwith a histidine.

Embodiment 39 is the pharmaceutical composition of embodiment 37,wherein the first antigen-binding domain comprises a light chainvariable domain of mirvetuximab with one or more amino acids substitutedwith a histidine.

Embodiment 40 the pharmaceutical composition of embodiment 37, whereinthe first antigen-binding domain comprises: a heavy chain variabledomain of mirvetuximab with one or more amino acids substituted with ahistidine; and a light chain variable domain of mirvetuximab with one ormore amino acids substituted with a histidine.

Embodiment 41 is the pharmaceutical composition of embodiment 38 or 40,wherein the heavy chain variable domain of mirvetuximab comprises SEQ IDNO: 1.

Embodiment 42 is the pharmaceutical composition of embodiment 39 or 40,wherein the light chain variable domain of mirvetuximab comprises SEQ IDNO: 2.

Embodiment 43 is the pharmaceutical composition of embodiment 37,wherein the first antigen-binding domain comprises a heavy chainvariable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs:3-5, respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 3-5 substituted with a histidine.

Embodiment 44 is the pharmaceutical composition of embodiment 37,wherein the first FOLR1-binding domain comprises a light chain variabledomain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 6-8 substituted with a histidine.

Embodiment 45 is the pharmaceutical composition of embodiment 37,wherein the first FOLR1-binding domain comprises: a heavy chain variabledomain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5,respectively, with collectively a total of one or more amino acidpositions in SEQ ID NOs: 3-5 substituted with a histidine; and a lightchain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ IDNOs: 6-8, respectively, with collectively a total of one or more aminoacid positions in SEQ ID NOs: 6-8 substituted with a histidine.

Embodiment 46 is the pharmaceutical composition of embodiment 37, 38, or43, wherein the first antigen-binding domain comprises a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29, 31, 32, 33, 34, 35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103,104, 105, and 107.

Embodiment 47 is the pharmaceutical composition of embodiment 37, 39, or44, wherein the first antigen-binding domain comprises a light chainvariable domain that is at least 90% identical to SEQ ID NO: 2, whereinthe light chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 2 selected from the group consisting of: 28, 30,31, 32, 34, 35, 36, 55, 93, 94, 95, 96, 97, 98, and 100.

Embodiment 48 is the pharmaceutical composition of embodiment 37, 38, or43, wherein the first antigen-binding domain comprises a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at two or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,54, 58, and 59.

Embodiment 49 is the pharmaceutical composition of embodiment 37, 40, or45, wherein the first antigen-binding domain comprises: a heavy chainvariable domain that is at least 90% identical to SEQ ID NO: 1, whereinthe heavy chain variable domain includes a histidine at one or morepositions in SEQ ID NO: 1 selected from the group consisting of: 24, 27,29, 31, 32, 33, 34, 35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103,104, 105, and 107; and a light chain variable domain that is at least90% identical to SEQ ID NO: 2, wherein the light chain variable domainincludes a histidine at one or more positions in SEQ ID NO: 2 selectedfrom the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 93, 94,95, 96, 97, 98, and 100.

Embodiment 50 is the pharmaceutical composition of embodiment 37,wherein the first antigen-binding domain comprises a heavy chainvariable domain of SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ IDNO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33,SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO:46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, or SEQID NO: 53.

Embodiment 51 is the pharmaceutical composition of embodiment 37 or 50,wherein the first antigen-binding domain comprises a light chainvariable domain of SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ IDNO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQID NO: 70, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79,SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 52 is the pharmaceutical composition of embodiment 37,wherein the first antigen-binding domain comprises a heavy chainvariable domain of SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ IDNO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97,SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO:102, or SEQ ID NO: 103.

Embodiment 53 is the pharmaceutical composition of embodiment 52,wherein the first antigen-binding domain comprises a light chainvariable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ IDNO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQID NO: 68, SEQ ID NO: 70, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78,SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 54 is the pharmaceutical composition of any one ofembodiments 37-53, wherein the composition provides for an increase intoxin liberation in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 55 is the pharmaceutical composition of embodiment 54,wherein the composition provides for at least a 20% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 56 is the pharmaceutical composition of embodiment 55,wherein the composition provides for at least a 50% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 57 is the pharmaceutical composition of embodiment 54,wherein the composition provides for at least a 2-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 58 is the pharmaceutical composition of embodiment 57,wherein the composition provides for at least a 5-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 59 is the pharmaceutical composition of any one ofembodiments 37-58, wherein the composition provides for an increase intarget mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC.

Embodiment 60 is the pharmaceutical composition of embodiment 59,wherein the composition provides for at least a 20% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 61 is the pharmaceutical composition of embodiment 60,wherein the composition provides for at least a 50% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 62 is the pharmaceutical composition of embodiment 59,wherein the composition provides for at least a 2-fold increase intarget mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC.

Embodiment 63 is the pharmaceutical composition of embodiment 62,wherein the composition provides for at least a 5-fold increase intarget mammalian cell killing as compared to a composition comprisingthe same amount of a control ABPC.

Embodiment 64 is the pharmaceutical composition of any one ofembodiments 37-63, wherein the composition provides for an increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 65 is the pharmaceutical composition of embodiment 64,wherein the composition provides for at least a 20% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 66 is the pharmaceutical composition of embodiment 65,wherein the composition provides for at least a 50% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 67 is the pharmaceutical composition of embodiment 64,wherein the composition provides for at least a 2-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 68 in the pharmaceutical composition of embodiment 67,wherein the composition provides for at least a 5-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 69 the pharmaceutical composition of any one of embodiments37-68, wherein the composition results in a less of a reduction in thelevel of FOLR1 presented on the surface of the target mammalian cell ascompared to a composition comprising the same amount of a control ABPC.

Embodiment 70 is the pharmaceutical composition of any one ofembodiments 37-68, wherein the composition does not result in adetectable reduction in the level of the FOLR1 presented on the surfaceof the target mammalian cell.

Embodiment 71 is the pharmaceutical composition of any one ofembodiments 1-70, wherein the target mammalian cell is a cancer cell.

Embodiment 72 is the pharmaceutical composition of any one ofembodiments 1-71, wherein the dissociation rate of the antigen-bindingdomain at a pH of about 4.0 to about 6.5 is at least 10% faster than thedissociation rate of the antigen-binding domain at a pH of about 7.0 toabout 8.0.

Embodiment 73 is the pharmaceutical composition of any one ofembodiments 1-71, wherein the dissociation rate of the antigen-bindingdomain at a pH of about 4.0 to about 6.5 is at least 3-fold faster thanthe dissociation rate of the antigen-binding domain at a pH of about 7.0to about 8.0.

Embodiment 74 is the pharmaceutical composition of any one ofembodiments 1-71, wherein the dissociation rate of the antigen-bindingdomain at a pH of about 4.0 to about 6.5 is at least 10-fold faster thanthe dissociation rate of the antigen-binding domain at a pH of about 7.0to about 8.0.

Embodiment 75 the pharmaceutical composition of any one of embodiments1-74, wherein the KD of the antigen-binding domain at a pH of about 4.0to about 6.5 is at least 10% greater than the KD of the antigen-bindingdomain at a pH of about 7.0 to about 8.0.

Embodiment 76 is the pharmaceutical composition of any one ofembodiments 1-74, wherein the KD of the antigen-binding domain at a pHof about 4.0 to about 6.5 is at least 3-fold greater than the KD of theantigen-binding domain at a pH of about 7.0 to about 8.0.

Embodiment 77 is the pharmaceutical composition of any one ofembodiments 1-74, wherein the KD of the antigen-binding domain at a pHof about 4.0 to about 6.5 is at least 10-fold greater than the KD of theantigen-binding domain at a pH of about 7.0 to about 8.0.

Embodiment 78 is the pharmaceutical composition of any one ofembodiments 1-77, wherein the ABPC is cytotoxic or cytostatic to thetarget mammalian cell.

Embodiment 79 is the pharmaceutical composition of any one ofembodiments 1-78, wherein the ABPC is cross-reactive with a non-humanprimate FOLR1 and human FOLR1.

Embodiment 80 is the pharmaceutical composition of any one ofembodiments 1-78, wherein the ABPC is cross-reactive with a non-humanprimate FOLR1, a human FOLR1, and one or both of rat FOLR1 and a mouseFOLR1.

Embodiment 81 is the pharmaceutical composition of embodiment 80,wherein the ABPC is cross-reactive with a non-human primate FOLR1, ahuman FOLR1, a rat FOLR1, and a mouse FOLR1.

Embodiment 82 is the pharmaceutical composition of any one ofembodiments 1-81, wherein the antigen-binding domain binds to an epitopeof FOLR1 that is present on the surface of cells from an Old WorldMonkey.

Embodiment 83 is the pharmaceutical composition of any one ofembodiments 1-82, wherein the ABPC comprises a single polypeptide.

Embodiment 84 the pharmaceutical composition of embodiment 83, whereinthe antigen-binding domain is selected from the group consisting of: aVH domain, a VHH domain, a VNAR domain, and a scFv.

Embodiment 85 is the pharmaceutical composition of embodiment 83 or 84,wherein the ABPC is a BiTe, a (scFv)2, a nanobody, a nanobody-HSA, aDART, a TandAb, a scDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, aHSAbody, scDiabody-HSA, or a tandem-scFv.

Embodiment 86 is the pharmaceutical composition of any one ofembodiments 1-82, wherein the ABPC comprises two or more polypeptides.

Embodiment 87 is the pharmaceutical composition of embodiment 86,wherein the ABPC is selected from the group of an antibody, a VHH-scAb,a VHH-Fab, a Dual scFab, a F(ab′)2, a diabody, a crossMab, a DAF(two-in-one), a DAF (four-in-one), a DutaMab, a DT-IgG, a knobs-in-holescommon light chain, a knobs-in-holes assembly, a charge pair, a Fab-armexchange, a SEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, aDVD-IgG, a IgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG,IgG(L,H)-Fv, IgG(H)-V, V(H)—IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab,2scFv-IgG, IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triplebody, a miniantibody, a minibody, a TriBi minibody, scFv-CH3 KIH,Fab-scFv, a F(ab′)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalentHCAb, a scDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandemVHH-Fc, a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, anImmTAC, an IgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, anAdnectin, a DARPin, a fibronectin, and a DEP conjugate.

Embodiment 88 is the pharmaceutical composition of any one ofembodiments 19-87, wherein at least one polypeptide of the ABPC isconjugated to the toxin, the radioisotope, the drug, or the smallmolecule via a cleavable linker.

Embodiment 89 is the pharmaceutical composition of any one ofembodiments 19-87, wherein at least one polypeptide of the ABPC isconjugated to the toxin, the radioisotope, the drug, or the smallmolecule via a non-cleavable linker.

Embodiment 90 is the pharmaceutical composition of any of embodiments1-89, wherein the half-life of the ABPC in vivo is decreased as comparedto the half-life of a control ABPC in vivo.

Embodiment 91 is the pharmaceutical composition of embodiment 90,wherein the half-life of the ABPC in vivo is decreased about 5% to about95% as compared to the half-life of a control ABPC in vivo.

Embodiment 92 is the pharmaceutical composition of embodiment 90,wherein the half-life of the ABPC in vivo is decreased about 10% toabout 95% as compared to the half-life of a control ABPC in vivo.

Embodiment 93 is the pharmaceutical composition of embodiment 90,wherein the half-life of the ABPC in vivo is decreased about 30% toabout 95% as compared to the half-life of a control ABPC in vivo.

Embodiment 94 is the pharmaceutical composition of embodiment 90,wherein the half-life of the ABPC in vivo is decreased about 50% toabout 95% as compared to the half-life of a control ABPC in vivo.

Embodiment 95 is the pharmaceutical composition of embodiment 90,wherein the half-life of the ABPC in vivo is decreased about 70% toabout 95% as compared to the half-life of a control ABPC in vivo.

Embodiment 96 is the pharmaceutical composition of any one ofembodiments 20-95, wherein the control ABPC is capable of specificallybinding to FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, wherein: (a) the control ABPC comprises a firstantigen-binding domain: (b) the dissociation rate of the firstantigen-binding domain of the control ABPC at a pH of about 4.0 to about6.5 is no more than 3-fold faster than the dissociation rate at a pH ofabout 7.0 to about 8.0; and (c) the dissociation constant (KD) of thefirst antigen-binding domain of the control ABPC at a pH of about 4.0 toabout 6.5 is no more than 3-fold greater than the KD at a pH of about7.0 to about 8.0.

Embodiment 97 is the pharmaceutical composition of any one ofembodiments 20-95, wherein the control ABPC is capable of specificallybinding to FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, wherein: (a) the control ABPC comprises a firstantigen-binding domain; (b) the dissociation rate of the firstantigen-binding domain of the control ABPC at a pH of about 4.0 to about6.5 is no more than 2-fold faster than the dissociation rate at a pH ofabout 7.0 to about 8.0; and (c) the dissociation constant (KD) of thefirst antigen-binding domain of the control ABPC at a pH of about 4.0 toabout 6.5 is no more than 2-fold greater than the KD at a pH of about7.0 to about 8.0.

Embodiment 98 is the pharmaceutical composition of any one ofembodiments 20-95, wherein the control ABPC is capable of specificallybinding to FOLR1 or an epitope of FOLR1 presented on the surface of atarget mammalian cell, wherein: (a) the control ABPC comprises a firstantigen-binding domain; (b) the dissociation rate of the firstantigen-binding domain of the control ABPC at a pH of about 4.0 to about6.5 is no more than 1-fold faster than the dissociation rate at a pH ofabout 7.0 to about 8.0; and (c) the dissociation constant (KD) of thefirst antigen-binding domain of the control ABPC at a pH of about 4.0 toabout 6.5 is no more than 1-fold greater than the KD at a pH of about7.0 to about 8.0.

Embodiment 99 is the pharmaceutical composition of any one ofembodiments 20-95, wherein the control ABPC is mirvetuximab.

Embodiment 100 is the pharmaceutical composition of any one ofembodiments 1-99, wherein the ABPC further comprises a secondantigen-binding domain.

Embodiment is a kit comprising at least one dose of the pharmaceuticalcomposition of any one of embodiments 1-100.

Embodiment 102 is an antigen-binding protein construct (ABPC)comprising: a first antigen-binding domain that is capable ofspecifically binding FOLR1 or an epitope of FOLR1 presented on thesurface of a target mammalian cell, wherein: (a) the dissociation rateof the first antigen-binding domain at a pH of about 4.0 to about 6.5 isfaster than the dissociation rate at a pH of about 7.0 to about 8.0; or(b) the dissociation constant (KD) of the first antigen-binding domainat a pH of about 4.0 to about 6.5 is greater than the KD at a pH ofabout 7.0 to about 8.0.

Embodiment 103 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises a heavy chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine.

Embodiment 104 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises a light chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine.

Embodiment 105 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises: a heavy chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine;and a light chain variable domain of mirvetuximab with one or more aminoacids substituted with a histidine.

Embodiment 106 is the ABPC of embodiment 103 or 105, wherein the heavychain variable domain of mirvetuximab comprises SEQ ID NO: 1.

Embodiment 107 is the ABPC of embodiment 104 or 105, wherein the lightchain variable domain of mirvetuximab comprises SEQ ID NO: 2.

Embodiment 108 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 3-5 substituted with a histidine.

Embodiment 109 is the ABPC of embodiment 102, wherein the firstFOLR1-binding domain comprises a light chain variable domain comprisinga CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, withcollectively a total of one or more amino acid positions in SEQ ID NOs:6-8 substituted with a histidine.

Embodiment is 110 is the ABPC of embodiment 102, wherein the firstFOLR1-binding domain comprises:

a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 ofSEQ ID NOs: 3-5, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 3-5 substituted with a histidine;and a light chain variable domain comprising a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 6-8, respectively, with collectively a total of one ormore amino acid positions in SEQ ID NOs: 6-8 substituted with ahistidine.

Embodiment 111 is the ABPC of embodiment 102, 103, or 108, wherein thefirst antigen-binding domain comprises a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34,35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103, 104, 105, and 107.

Embodiment 112 is the ABPC of embodiment 102, 104, or 109, wherein thefirst antigen-binding domain comprises a light chain variable domainthat is at least 90% identical to SEQ ID NO: 2, wherein the light chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 2 selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36,55, 93, 94, 95, 96, 97, 98, and 100.

Embodiment 113 is the ABPC of embodiment 102, 103, or 108, wherein thefirst antigen-binding domain comprises a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at two or more positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 54, 58, and 59.

Embodiment 114 is the ABPC of embodiment 102, 105, or 110, wherein thefirst antigen-binding domain comprises: a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34,35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103, 104, 105, and 107;and a light chain variable domain that is at least 90% identical to SEQID NO: 2, wherein the light chain variable domain includes a histidineat one or more positions in SEQ ID NO: 2 selected from the groupconsisting of: 28, 30, 31, 32, 34, 35, 36, 55, 93, 94, 95, 96, 97, 98,and 100.

Embodiment 115 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 28,SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO:35, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, or SEQ ID NO: 53.

Embodiment 116 is the ABPC of embodiment 102 or 115, wherein the firstantigen-binding domain comprises a light chain variable domain of SEQ IDNO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70,SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO:80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 117 is the ABPC of embodiment 102, wherein the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94,SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103.

Embodiment 118 is the ABPC of embodiment 117, wherein the firstantigen-binding domain comprises a light chain variable domain of SEQ IDNO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 76,SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO:81, or SEQ ID NO: 83.

Embodiment 119 is the ABPC of any one of embodiments 102-118, whereinthe ABPC is degraded in the target mammalian cell followinginternalization of the ABPC by the target mammalian cell.

Embodiment 120 is the ABPC of any one of embodiments 102-119, whereinthe ABPC further comprises a conjugated toxin, radioisotope, drug, orsmall molecule.

Embodiment 121 is the ABPC of embodiment 120, wherein a compositioncomprising the ABPC provides for an increase in toxin liberation in thetarget mammalian cell as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 122 is the ABPC of embodiment 121, wherein a compositioncomprising the ABPC provides for at least a 20% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 123 is the ABPC of embodiment 122, wherein a compositioncomprising the ABPC provides for at least a 50% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 124 is the ABPC of embodiment 121, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 125 is the ABPC of embodiment 124, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 126 is the ABPC of any one of embodiments 120-125, wherein acomposition comprising the ABPC provides for an increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 127 is the ABPC of embodiment 126, wherein a compositioncomprising the ABPC provides for at least a 20% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 128 is the ABPC of embodiment 127, wherein a compositioncomprising the ABPC provides for at least a 50% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 129 is the ABPC of embodiment 126, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 130 is the ABPC of embodiment 129, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 131 is the ABPC of any one of embodiments 102-130, wherein acomposition comprising the ABPC provides for an increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 132 is the ABPC of embodiment 131, wherein a compositioncomprising the ABPC provides for at least a 20% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 133 is the ABPC of embodiment 132, wherein a compositioncomprising the ABPC provides for at least a 50% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 134 is the ABPC of embodiment 131, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 135 is the ABPC of embodiment 134, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 136 is the ABPC of any one of embodiments 102-135, wherein acomposition comprising the ABPC results in a less of a reduction in thelevel of FOLR1 presented on the surface of the target mammalian cell ascompared to a composition comprising the same amount of a control ABPC.

Embodiment 137 is the ABPC of any one of embodiments 102-135; wherein acomposition comprising the ABPC does not result in a detectablereduction in the level of the FOLR1 presented on the surface of thetarget mammalian cell.

Embodiment 138 is an antigen-binding protein construct (ABPC)comprising: a first antigen-binding domain that is capable ofspecifically binding FOLR1 or an epitope of FOLR1 presented on thesurface of a target mammalian cell; and a conjugated toxin,radioisotope, drug, or small molecule, wherein: (a) the dissociationrate of the first antigen-binding domain at a pH of about 4.0 to about6.5 is faster than the dissociation rate at a pH of about 7.0 to about8.0; or the dissociation constant (KD) of the first antigen-bindingdomain at a pH of about 4.0 to about 6.5 is greater than the KD at a pHof about 7.0 to about 8.0; and (b) the composition provides for one ormore of: an increase in toxin liberation in the target mammalian cell ascompared to a composition comprising the same amount of a control ABPC;an increase in target mammalian cell killing as compared to acomposition comprising the same amount of a control BPC; and an increasein endolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 139 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises a heavy chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine.

Embodiment 140 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises a light chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine.

Embodiment 141 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises:

a heavy chain variable domain of mirvetuximab with one or more aminoacids substituted with a histidine; and a light chain variable domain ofmirvetuximab with one or more amino acids substituted with a histidine.

Embodiment 142 is the ABPC of embodiment 139 or 141, wherein the heavychain variable domain of mirvetuximab comprises SEQ ID NO: 1.

Embodiment 143 is the ABPC of embodiment 140 or 141, wherein the lightchain variable domain of mirvetuximab comprises SEQ ID NO: 2.

Embodiment 144 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises a heavy chain variable domaincomprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively,with collectively a total of one or more amino acid positions in SEQ IDNOs: 3-5 substituted with a histidine.

Embodiment 145 is the ABPC of embodiment 138, wherein the firstFOLR1-binding domain comprises a light chain variable domain comprisinga CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, withcollectively a total of one or more amino acid positions in SEQ ID NOs:6-8 substituted with a histidine.

Embodiment 146 is the ABPC of embodiment 138, wherein the firstFOLR1-binding domain comprises:

a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 ofSEQ ID NOs: 3-5, respectively, with collectively a total of one or moreamino acid positions in SEQ ID NOs: 3-5 substituted with a histidine;and a light chain variable domain comprising a CDR1, a CDR2, and a CDR3of SEQ ID NOs: 6-8, respectively, with collectively a total of one ormore amino acid positions in SEQ ID NOs: 6-8 substituted with ahistidine.

Embodiment 147 is the ABPC of embodiment 138, 139, or 144, wherein thefirst antigen-binding domain comprises a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34,35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103, 104, 105, and 107.

Embodiment 148 is the ABPC of embodiment 138, 140, or 145, wherein thefirst antigen-binding domain comprises a light chain variable domainthat is at least 90% identical to SEQ ID NO: 2, wherein the light chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 2 selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36,55, 93, 94, 95, 96, 97, 98, and 100.

Embodiment 149 is the ABPC of embodiment 138, 139, or 144, wherein thefirst antigen-binding domain comprises a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at two more positions in SEQ ID NO:1 selected from the group consisting of: 24, 27, 54, 58, and 59.

Embodiment 150 is the ABPC of embodiment 138, 141, or 146, wherein thefirst antigen-binding domain comprises: a heavy chain variable domainthat is at least 90% identical to SEQ ID NO: 1, wherein the heavy chainvariable domain includes a histidine at one or more positions in SEQ IDNO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34,35, 50, 54, 55, 57, 58, 59, 97, 99, 100, 102, 103, 104, 105, and 107;and a light chain variable domain that is at least 90% identical to SEQID NO: 2, wherein the light chain variable domain includes a histidineat one or more positions in SEQ ID NO: 2 selected from the groupconsisting of: 28, 30, 31, 32, 34, 35, 36, 55, 93, 94, 95, 96, 97, 98,and 100.

Embodiment 151 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 28,SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO:35, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ IDNO: 49, SEQ ID NO: 50, SEQ ID NO: 51, or SEQ ID NO: 53.

Embodiment 152 is the ABPC of embodiment 138 or 151, wherein the firstantigen-binding domain comprises a light chain variable domain of SEQ IDNO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 76,SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO:81, or SEQ ID NO: 83.

Embodiment 153 is the ABPC of embodiment 138, wherein the firstantigen-binding domain comprises a heavy chain variable domain of SEQ IDNO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94,SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103.

Embodiment 154 is the ABPC of embodiment 153, wherein the firstantigen-binding domain comprises a light chain variable domain of SEQ IDNO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70,SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO:80, SEQ ID NO: 81, or SEQ ID NO: 83.

Embodiment 155 is the ABPC of any one of embodiments 138-154, wherein acomposition comprising the ABPC provides for an increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 156 is the ABPC of embodiment 155, wherein a compositioncomprising the ABPC provides for at least a 20% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 157 is the ABPC of embodiment 156, wherein a compositioncomprising the ABPC provides for at least a 50% increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 158 is the ABPC of embodiment 155, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase in toxinliberation in the target mammalian cell as compared to a

Embodiment 159 is the ABPC of embodiment 158, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase in toxinliberation in the target mammalian cell as compared to a compositioncomprising the same amount of a control ABPC.

Embodiment 160 is the ABPC of any one of embodiments 138-159; wherein acomposition comprising the ABPC provides for an increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 161 is the ABPC of embodiment 160, wherein a compositioncomprising the ABPC provides for at least a 20% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 162 is the ABPC of embodiment 161, wherein a compositioncomprising the ABPC provides for at least a 50% increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 163 is the ABPC of embodiment 160, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 164 is the ABPC of embodiment 163, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase in targetmammalian cell killing as compared to a composition comprising the sameamount of a control ABPC.

Embodiment 165 is the ABPC of any one of embodiments 138-164, wherein acomposition comprising the ABPC provides for an increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 166 is the ABPC of embodiment 165, wherein a compositioncomprising the ABPC provides for at least a 20% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 167 is the ABPC of embodiment 166, wherein a compositioncomprising the ABPC provides for at least a 50% increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 168 is the ABPC of embodiment 165, wherein a compositioncomprising the ABPC provides for at least a 2-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 169 is the ABPC of embodiment 168, wherein a compositioncomprising the ABPC provides for at least a 5-fold increase inendolysosomal delivery in the target mammalian cell as compared to acomposition comprising the same amount of a control ABPC.

Embodiment 170 is the ABPC of any one of embodiments 138-169, wherein acomposition comprising the ABPC results in a less of a reduction in thelevel of FOLR1 presented on the surface of the target mammalian cell ascompared to a composition comprising the same amount of a control ABPC.

Embodiment 171 is the ABPC of any one of embodiments 138-169, wherein acomposition comprising the ABPC does not result in a detectablereduction in the level of the FOLR1 presented on the surface of thetarget mammalian cell.

Embodiment 172 is the ABPC of any one of embodiments 102-171, whereinthe target mammalian cell is a cancer cell.

Embodiment 173 is the ABPC of any one of embodiments 102-172, whereinthe dissociation rate of the antigen-binding domain at a pH of about 4.0to about 6.5 is at least 10% faster than the dissociation rate of theantigen-binding domain at a pH of about 7.0 to about 8.0.

Embodiment 174 is the ABPC of any one of embodiments 102-172, whereinthe dissociation rate of the antigen-binding domain at a pH of about 4.0to about 6.5 is at least 3-fold faster than the dissociation rate of theantigen-binding domain at a pH of about 7.0 to about 8.0.

Embodiment 175 is the ABPC of any one of embodiments 102-172, whereinthe dissociation rate of the antigen-binding domain at a pH of about 4.0to about 6.5 is at least 10-fold faster than the dissociation rate ofthe antigen-binding domain at a pH of about 7.0 to about 8.0.

Embodiment 176 is the ABPC of any one of embodiments 102-175, whereinthe KD of the antigen-binding domain at a pH of about 4.0 to about 6.5is at least 10% greater than the KD of the antigen-binding domain at apH of about 7.0 to about 8.0.

Embodiment 177 is the ABPC of any one of embodiments 102-175, whereinthe KD of the antigen-binding domain at a pH of about 4.0 to about 6.5is at least 3-fold greater than the KD of the antigen-binding domain ata pH of about 7.0 to about 8.0.

Embodiment 178 is the ABPC of any one of embodiments 102-175, whereinthe KD of the antigen-binding domain at a pH of about 4.0 to about 6.5is at least 10-fold greater than the KD of the antigen-binding domain ata pH of about 7.0 to about 8.0.

Embodiment 179 is the ABPC of any one of embodiments 102-178, whereinthe ABPC is cytotoxic or cytostatic to the target mammalian cell.

Embodiment 180 is the ABPC of any one of embodiments 102-179, whereinthe ABPC is cross-reactive with a non-human primate FOLR1 and humanFOLR1.

Embodiment 181 is the pharmaceutical composition of any one ofembodiments 102-179, wherein the ABPC is cross-reactive with a non-humanprimate FOLR1, a human FOLR1, and one or both of rat FOLR1 and a mouseFOLR1.

Embodiment 182 is the pharmaceutical composition of embodiment 181,wherein the ABPC is cross-reactive with a non-human primate FOLR1, ahuman FOLR1, a rat FOLR1, and a mouse FOLR1.

Embodiment 183 is the ABPC of any one of embodiments 102-182, whereinthe antigen-binding domain binds to an epitope of FOLR1 that is presenton the surface of cells from an Old World Monkey.

Embodiment 184 is the ABPC of any one of embodiments 102-183, whereinthe ABPC comprises a single polypeptide.

Embodiment 185 is the ABPC of embodiment 184, wherein theantigen-binding domain is selected from the group consisting of: a VHdomain, a VHH domain, a VNAR domain, and a scFv.

Embodiment 186 is the ABPC of embodiment 184 or 185, wherein the ABPC isa BiTe, a (scFv)2, a nanobody, a nanobody-HSA, a DART, a TandAb, ascDiabody, a scDiabody-CH3, scFv-CH-CL-scFv, a HSAbody, scDiabody-HSA,or a tandem-scFv.

Embodiment 187 is the ABPC of any one of embodiments 102-183, whereinthe ABPC comprises two or more polypeptides.

Embodiment 188 is the ABPC of embodiment 187, wherein the ABPC isselected from the group of an antibody, a VHH-scAb, a VHH-Fab, a DualscFab, a F(ab′)2, a diabody, a crossMab, a DAF (two-in-one), a DAF(four-in-one), a DutaMab, a DT-IgG, a knobs-in-holes common light chain,a knobs-in-holes assembly, a charge pair, a Fab-arm exchange, aSEEDbody, a LUZ-Y, a Fcab, a κλ-body, an orthogonal Fab, a DVD-IgG, aIgG(H)-scFv, a scFv-(H)IgG, IgG(L)-scFv, scFv-(L)IgG, IgG(L,H)-Fv,IgG(H)-V, V(H)—IgG, IgG(L)-V, V(L)-IgG, KIH IgG-scFab, 2scFv-IgG,IgG-2scFv, scFv4-Ig, Zybody, DVI-IgG, Diabody-CH3, a triple body, aminiantibody, a minibody, a TriBi minibody, scFv-CH3 KIH, Fab-scFv, aF(ab′)2-scFv2, a scFv-KIH, a Fab-scFv-Fc, a tetravalent HCAb, ascDiabody-Fc, a Diabody-Fc, a tandem scFv-Fc, a VHH-Fc, a tandem VHH-Fc,a VHH-Fc KiH, a Fab-VHH-Fc, an Intrabody, a dock and lock, an ImmTAC, anIgG-IgG conjugate, a Cov-X-Body, a scFv1-PEG-scFv2, an Adnectin, aDARPin, a fibronectin, and a DEP conjugate.

Embodiment 189 is the ABPC of any one of embodiments 120-188, wherein atleast one polypeptide of the ABPC is conjugated to the toxin, theradioisotope, the drug, or the small molecule via a cleavable linker.

Embodiment 190 is the ABPC of any one of embodiments 120-188, wherein atleast one polypeptide of the ABPC is conjugated to the toxin, theradioisotope, the drug, or the small molecule via a non-cleavablelinker.

Embodiment 191 is the ABPC of any of embodiments 102-190, wherein thehalf-life of the ABPC in vivo is decreased as compared to the half-lifeof a control ABPC in vivo.

Embodiment 192 is the ABPC of embodiment 191, wherein the half-life ofthe ABPC in vivo is decreased about 5% to about 95% as compared to thehalf-life of a control ABPC in vivo.

Embodiment 193 is the ABPC of embodiment 191, wherein the half-life ofthe ABPC in vivo is decreased about 10% to about 95% as compared to thehalf-life of a control ABPC in vivo.

Embodiment 194 the ABPC of embodiment 191, wherein the half-life of theABPC in vivo is decreased about 30% to about 95% as compared to thehalf-life of a control ABPC in vivo.

Embodiment 195 is the ABPC of embodiment 191, wherein the half-life ofthe ABPC in vivo is decreased about 50% to about 95% as compared to thehalf-life of a control ABPC in vivo.

Embodiment 196 is the ABPC of embodiment 191, wherein the half-life ofthe ABPC in vivo is decreased about 70% to about 95% as compared to thehalf-life of a control ABPC in vivo.

Embodiment 197 is the ABPC of any one of embodiments 121-196, whereinthe control ABPC is capable of specifically binding to FOLR1 or anepitope of FOLR1 presented on the surface of a target mammalian cell,wherein: (a) the control ABPC comprises a first antigen-binding domain;(b) the dissociation rate of the first antigen-binding domain of thecontrol ABPC at a pH of about 4.0 to about 6.5 is no more than 3-foldfaster than the dissociation rate at a pH of about 7.0 to about 8.0; and(c) the dissociation constant (KD) of the first antigen-binding domainof the control ABPC at a pH of about 4.0 to about 6.5 is no more than3-fold greater than the KD at a pH of about 7.0 to about 8.0.

Embodiment 198 is the ABPC of any one of embodiments 121-196, whereinthe control ABPC is capable of specifically binding to FOLR1 or anepitope of FOLR1 presented on the surface of a target mammalian cell,wherein: (a) the control ABPC comprises a first antigen-binding domain;(b) the dissociation rate of the first antigen-binding domain of thecontrol ABPC at a pH of about 4.0 to about 6.5 is no more than 2-foldfaster than the dissociation rate at a pH of about 7.0 to about 8.0; and(c) the dissociation constant (KD) of the first antigen-binding domainof the ABPC at a pH of about 4.0 to about 6.5 is no more than 2-foldgreater than the KD at a pH of about 7.0 to about 8.0.

Embodiment 199 is the ABPC of any one of embodiments 121-196, whereinthe control ABPC is capable of specifically binding to FOLR1 or anepitope of FOLR1 presented on the surface of a target mammalian cell,wherein: (a) the control ABPC comprises a first antigen-binding domain;(b) the dissociation rate of the first antigen-binding domain of thecontrol ABPC at a pH of about 4.0 to about 6.5 is no more than 1-foldfaster than the dissociation rate at a pH of about 7.0 to about 8.0; and(c) the dissociation constant (KD) of the first antigen-binding domainof the control ABPC at a pH of about 4.0 to about 6.5 is no more than1-fold greater than the KD at a pH of about 7.0 to about 8.0.

Embodiment 200 is the ABPC of any one of embodiments 121-196, whereinthe control ABPC is mirvetuximab.

Embodiment 201 is the ABPC of any one of embodiments 102-200, whereinthe ABPC further comprises a second antigen-binding domain.

Embodiment 202 is a kit comprising at least one dose of the ABPC of anyone of embodiments 102-201.

Embodiment 203 is a method of treating a cancer characterized by havinga population of cancer cells that have FOLR1 or an epitope of FOLR1presented on their surface, the method comprising:

administering a therapeutically effective amount of the pharmaceuticalcomposition of any one of embodiments 1-100 or the ABPC of any one ofembodiments 102-201 to a subject identified as having a cancercharacterized by having the population of cancer cells.

Embodiment 204 is a method of reducing the volume of a tumor in asubject, wherein the tumor is characterized by having a population ofcancer cells that have FOLR1 or an epitope of FOLR1 presented on theirsurface, the method comprising: administering a therapeuticallyeffective amount of the pharmaceutical composition of any one ofembodiments 1-100 or the ABPC of any one of embodiments 102-201 to asubject identified as having a cancer characterized by having thepopulation of cancer cells.

Embodiment 205 is a method of inducing cell death in a cancer cell in asubject, wherein the cancer cell has FOLR1 or an epitope of FOLR1presented on its surface, wherein the method comprises:

administering a therapeutically effective amount of the pharmaceuticalcomposition of any one of embodiments 1-98 or the ABPC of any one ofembodiments 102-201 to a subject identified as having a cancercharacterized by having a population of the cancer cells.

Embodiment 206 is the method of any one of embodiments 203-205, whereinthe cancer is a primary tumor.

Embodiment 207 is the method of any one of embodiments 203-205, whereinthe cancer is a metastasis.

Embodiment 208 is the method of any one of embodiments 203-207, whereinthe cancer is a non-T-cell-infiltrating tumor.

Embodiment 209 is the method of any one of embodiments 203-207, whereinthe cancer is a T-cell infiltrating tumor.

Embodiment 210 is a method of decreasing the risk of developing ametastasis or decreasing the risk of developing an additional metastasisin a subject having a cancer, wherein the cancer is characterized byhaving a population of cancer cells that have FOLR1 or an epitope ofFOLR1 presented on their surface the method comprising: administering atherapeutically effective amount of the pharmaceutical composition ofany one of embodiments 1-100 or the ABPC of any one of embodiments102-201 to a subject identified as having a cancer characterized byhaving the population of cancer cells.

Embodiment 211 is the method of embodiment 210, wherein the cancer is anon-T-cell-infiltrating tumor.

Embodiment 212 is the method of embodiment 210, wherein the cancer is aT-cell infiltrating tumor.

Other Embodiments

It is to be understood that while the invention has been described inconjunction with the detailed description thereof, the foregoingdescription is intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims. Otheraspects, advantages, and modifications are within the scope of thefollowing claims.

Sequence Appendix >Heavy Chain of mirvetuximab IgG (SEQ ID NO: 1)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Light Chain of mirvetuximab IgG (SEQ ID NO: 2)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Heavy Chain CDR1 of mirvetuximab(SEQ ID NO: 3) KASGYTFTGYFMN >Heavy Chain CDR2 of mirvetuximab(SEQ ID NO: 4) RIHPYDGDTFYNQKFQG >Heavy Chain CDR3 of mirvetuximab(SEQ ID NO: 5) TRYDGSRAMDY >Light Chain CDR1 of mirvetuximab(SEQ ID NO: 6) KASQSVSFAGTSLMH >Light Chain CDR2 of mirvetuximab(SEQ ID NO: 7) RASNLEA >Light Chain CDR3 of mirvetuximab (SEQ ID NO: 8)QQSREYPYT >Mature Human FOLR1 (SEQ ID NO: 9)RIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPWRKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQVDQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHFYFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAM >cDNA Encoding Mature Human FOLR1(SEQ ID NO: 10) ATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTGTGGGTGGCTGTAGTAGGGGAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCTGCATGAACGCCAAGCACCACAAGGAAAAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACCCTGGAGGAAGAATGCCTGCTGTTCTACCAACACCAGCCAGGAAGCCCATAAGGATGTTTCCTACCTATATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCAAACGGCATTTCATCCAGGACACCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTGGATCAGAGCTGGCGCAAAGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAGCAATGGTGGGAAGATTGTCGCACCTCCTACACCTGCAAGAGCAACTGGCACAAGGGCTGGAACTGGACTTCAGGGTTTAACAAGTGCGCAGTGGGAGCTGCCTGCCAACCTTTCCATTTCTACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTGGACTCACTCCTACAAGGTCAGCAACTACAGCCGAGGGAGTGGCCGCTGCATCCAGATGTGGTTCGACCCAGCCCAGGGCAACCCCAATGAGGAGGTGGCGAGGTTCTATGCTGCAGCCATGAGTGGGGCTGGGCCCTGGGCAGCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCAGC >Extracellular Domain of FOLR1(SEQ ID NO: 11) RIAWARTELLNVCMNAKHHKEKPGPEDKLHEQCRPWRKNACCSTNTSQEAHKDVSYLYRFNWNHCGEMAPACKRHFIQDTCLYECSPNLGPWIQQVDQSWRKERVLNVPLCKEDCEQWWEDCRTSYTCKSNWHKGWNWTSGFNKCAVGAACQPFHFYFPTPTVLCNEIWTHSYKVSNYSRGSGRCIQMWFDPAQGNPNEEVARFYAAAM >cDNA Encoding Extracellular Domain of FOLR1(SEQ ID NO: 12) ATGGCTCAGCGGATGACAACACAGCTGCTGCTCCTTCTAGTGTGGGTGGCTGTAGTAGGGGAGGCTCAGACAAGGATTGCATGGGCCAGGACTGAGCTTCTCAATGTCTGCATGAACGCCAAGCACCACAAGGAAAAGCCAGGCCCCGAGGACAAGTTGCATGAGCAGTGTCGACCCTGGAGGAAGAATGCCTGCTGTTCTACCAACACCAGCCAGGAAGCCCATAAGGATGTTTCCTACCTATATAGATTCAACTGGAACCACTGTGGAGAGATGGCACCTGCCTGCAAACGGCATTTCATCCAGGACACCTGCCTCTACGAGTGCTCCCCCAACTTGGGGCCCTGGATCCAGCAGGTGGATCAGAGCTGGCGCAAAGAGCGGGTACTGAACGTGCCCCTGTGCAAAGAGGACTGTGAGCAATGGTGGGAAGATTGTCGCACCTCCTACACCTGCAAGAGCAACTGGCACAAGGGCTGGAACTGGACTTCAGGGTTTAACAAGTGCGCAGTGGGAGCTGCCTGCCAACCTTTCCATTTCTACTTCCCCACACCCACTGTTCTGTGCAATGAAATCTGGACTCACTCCTACAAGGTCAGCAACTACAGCCGAGGGAGTGGCCGCTGCATCCAGATGTGGTTCGACCCAGCCCAGGGCAACCCCAATGAGGAGGTGGCGAGGTTCTATGCTGCAGCCATGAGTGGGGCTGGGCCCTGGGCAGCCTGGCCTTTCCTGCTTAGCCTGGCCCTAATGCTGCTGTGGCTGCTCAGC >Heavy Chain of mirvetuximab IgG histidine scanningvariant #1 (SEQ ID NO: 13)QVQLVQSGAEVVKPGASVKISCHASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #2(SEQ ID NO: 14)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #3(SEQ ID NO: 15)QVQLVQSGAEVVKPGASVKISCKAHGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #4(SEQ ID NO: 16)QVQLVQSGAEVVKPGASVKISCKASHYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #5(SEQ ID NO: 17)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #6(SEQ ID NO: 18)QVQLVQSGAEVVKPGASVKISCKASGYHFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #7(SEQ ID NO: 19)QVQLVQSGAEVVKPGASVKISCKASGYTHTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #8(SEQ ID NO: 20)QVQLVQSGAEVVKPGASVKISCKASGYTFHGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #9(SEQ ID NO: 21)QVQLVQSGAEVVKPGASVKISCKASGYTFTHYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #10(SEQ ID NO: 22)QVQLVQSGAEVVKPGASVKISCKASGYTFTGHFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #11(SEQ ID NO: 23)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYHMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #12(SEQ ID NO: 24)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFHNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #13(SEQ ID NO: 25)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMHWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #14(SEQ ID NO: 26)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGHIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #15(SEQ ID NO: 27)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRHHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #16(SEQ ID NO: 28)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIAPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #17(SEQ ID NO: 29)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHHYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #18(SEQ ID NO: 30)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #19(SEQ ID NO: 31)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYHGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #20(SEQ ID NO: 32)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDHDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #21(SEQ ID NO: 33)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGHTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #22(SEQ ID NO: 34)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #23(SEQ ID NO: 35)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #24(SEQ ID NO: 36)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFHNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #25(SEQ ID NO: 37)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYHQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #26(SEQ ID NO: 38)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNHKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #27(SEQ ID NO: 39)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQHFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #28(SEQ ID NO: 40)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKHQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #29(SEQ ID NO: 41)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFHGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #30(SEQ ID NO: 42)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQHKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #31(SEQ ID NO: 43)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCHRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #32(SEQ ID NO: 44)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTHYDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #33(SEQ ID NO: 45)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRHDGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #34(SEQ ID NO: 46)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYHGSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #35(SEQ ID NO: 47)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDHSRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #36(SEQ ID NO: 48)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGHRAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #37(SEQ ID NO: 49)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSHAMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #38(SEQ ID NO: 50)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRHMDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #39(SEQ ID NO: 51)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAHDYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #40(SEQ ID NO: 52)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMHYWGQGTTVTVSS >Heavy Chain of mirvetuximab IgG histidine scanning variant #41(SEQ ID NO: 53)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDHWGQGTTVTVSS >Light Chain of mirvetuximab IgG histidine scanning variant #1(SEQ ID NO: 54)DIVLTQSPLSLAVSLGQPAIISCHASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #2 (SEQ ID NO: 55)DIVLTQSPLSLAVSLGQPAIISCKHSQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #3 (SEQ ID NO: 56)DIVLTQSPLSLAVSLGQPAIISCKAHQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #4 (SEQ ID NO: 57)DIVLTQSPLSLAVSLGQPAIISCKASHSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #5 (SEQ ID NO: 58)DIVLTQSPLSLAVSLGQPAIISCKASQHVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #6 (SEQ ID NO: 59)DIVLTQSPLSLAVSLGQPAIISCKASQSHSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #7 (SEQ ID NO: 60)DIVLTQSPLSLAVSLGQPAIISCKASQSVHFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #8 (SEQ ID NO: 61)DIVLTQSPLSLAVSLGQPAIISCKASQSVSHAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #9 (SEQ ID NO: 62)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFHGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #10 (SEQ ID NO: 63)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAHTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #11 (SEQ ID NO: 64)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGHSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #12 (SEQ ID NO: 65)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTHLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #13 (SEQ ID NO: 66)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSHMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #14 (SEQ ID NO: 67)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLHHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #15 (SEQ ID NO: 68)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMAWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #16 (SEQ ID NO: 69)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYHASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #17 (SEQ ID NO: 70)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRHSNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #18 (SEQ ID NO: 71)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRAHNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #19 (SEQ ID NO: 72)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASHLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #20 (SEQ ID NO: 73)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNHEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #21 (SEQ ID NO: 74)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLHAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #22 (SEQ ID NO: 75)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEHGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #23 (SEQ ID NO: 76)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCHQSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #24 (SEQ ID NO: 77)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQHSREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #25 (SEQ ID NO: 78)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQHREYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #26 (SEQ ID NO: 79)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSHEYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #27 (SEQ ID NO: 80)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSRHYPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #28 (SEQ ID NO: 81)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREHPYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #29 (SEQ ID NO: 82)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYHYTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #30 (SEQ ID NO: 83)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPHTFGGGTKLEIK >Light Chain of mirvetuximab IgG histidine scanningvariant #31 (SEQ ID NO: 84)DIVLTQSPLSLAVSLGQPAIISCKASQSVSFAGTSLMHWYHQKPGQQPRLLIYRASNLEAGVPDRFSGSGSKTDFTLTISPVEAEDAATYYCQQSREYPYHFGGGTKLEIK >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #1 (SEQ ID NO: 85)QVQLVQSGAEVVKPGASVKISCKHSGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #2 (SEQ ID NO: 86)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #3 (SEQ ID NO: 87)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #4 (SEQ ID NO: 88)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #5 (SEQ ID NO: 89)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #6 (SEQ ID NO: 90)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #7 (SEQ ID NO: 91)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #8 (SEQ ID NO: 92)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #9 (SEQ ID NO: 93)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #10 (SEQ ID NO: 94)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDHHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #11 (SEQ ID NO: 95)QVQLVQSGAEVVKPGASVKISCKHSGHTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #12 (SEQ ID NO: 96)QVQLVQSGAEVVKPGASVKISCKHSGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #13 (SEQ ID NO: 97)QVQLVQSGAEVVKPGASVKISCKHSGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #14 (SEQ ID NO: 98)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #15 (SEQ ID NO: 99)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #16 (SEQ ID NO: 100)QVQLVQSGAEVVKPGASVKISCKHSGYTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDFIHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #17 (SEQ ID NO: 101)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDHFYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #18 (SEQ ID NO: 102)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDTHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #19 (SEQ ID NO: 103)QVQLVQSGAEVVKPGASVKISCKASGHTFTGYFMNWVKQSPGQSLEWIGRIHPYDGDFIHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain Combinations of mirvetuximab IgG histidinescanning variant #20 (SEQ ID NO: 104)QVQLVQSGAEVVKPGASVKISCKASGYTFTGYFMNWVKQSPGQSLEWIGRIHPHDGDFIHYNQKFQGKATLTVDKSSNTAHMELLSLTSEDFAVYYCTRYDGSRAMDYWGQGTTVTVSS >Heavy Chain of STRO-002 IgG (SEQ ID NO: 105)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Light Chain of STRO-022 IgG (SEQ ID NO: 106)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Heavy Chain CDR1 of STRO-002(SEQ ID NO: 107) GFNIRTQSIH >Heavy Chain CDR2 of STRO-002(SEQ ID NO: 108) DIFPIDGITDYADSVKG >Heavy Chain CDR3 of STRO-002(SEQ ID NO: 109) ARGSWSWPSGMDYYLDY >Light Chain CDR1 of STRO-002(SEQ ID NO: 110) RASQDVNTAVA >Light Chain CDR2 of STRO-002(SEQ ID NO: 111) SASFLYS >Light Chain CDR3 of STRO-002 (SEQ ID NO: 112)QQHYTTPPT >Heavy Chain of STRO-002 IgG histidine scanning variant #1(SEQ ID NO: 113)EVQLVESGGGLVQPGGSLRLSCAASHFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #2(SEQ ID NO: 114)EVQLVESGGGLVQPGGSLRLSCAASGHNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #3(SEQ ID NO: 115)EVQLVESGGGLVQPGGSLRLSCAASGFHIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #4(SEQ ID NO: 116)EVQLVESGGGLVQPGGSLRLSCAASGFNHRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #5(SEQ ID NO: 117)EVQLVESGGGLVQPGGSLRLSCAASGFNIHTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #6(SEQ ID NO: 118)EVQLVESGGGLVQPGGSLRLSCAASGFNIRHQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #7(SEQ ID NO: 119)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTHSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #8(SEQ ID NO: 120)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQHIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #9(SEQ ID NO: 121)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSHHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #10(SEQ ID NO: 122)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIAWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #11(SEQ ID NO: 123)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGHIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #12(SEQ ID NO: 124)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDHFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #13(SEQ ID NO: 125)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIHPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #14(SEQ ID NO: 126)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFHIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #15(SEQ ID NO: 127)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPHDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #16(SEQ ID NO: 128)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIHGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #17(SEQ ID NO: 129)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDHITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #18(SEQ ID NO: 130)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGHTDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #19(SEQ ID NO: 131)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGIHDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #20(SEQ ID NO: 132)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITHYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #21(SEQ ID NO: 133)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDHADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #22(SEQ ID NO: 134)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYHDSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #23(SEQ ID NO: 135)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYAHSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #24(SEQ ID NO: 136)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADHVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #25(SEQ ID NO: 137)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSHKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #26(SEQ ID NO: 138)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVHGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #27(SEQ ID NO: 139)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKHRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #28(SEQ ID NO: 140)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCHRGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #29(SEQ ID NO: 141)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAHGSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #30(SEQ ID NO: 142)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHSWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #31(SEQ ID NO: 143)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGHWSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #32(SEQ ID NO: 144)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSHSWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #33(SEQ ID NO: 145)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWHWPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #34(SEQ ID NO: 146)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSHPSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #35(SEQ ID NO: 147)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWHSGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #36(SEQ ID NO: 148)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPHGMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #37(SEQ ID NO: 149)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSHMDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #38(SEQ ID NO: 150)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGHDYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #39(SEQ ID NO: 151)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMHYYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #40(SEQ ID NO: 152)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDHYLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #41(SEQ ID NO: 153)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYHLDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #42(SEQ ID NO: 154)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYHDYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #43(SEQ ID NO: 155)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLHYWGQGTLVTVSS >Heavy Chain of STRO-002 IgG histidine scanning variant #44(SEQ ID NO: 156)EVQLVESGGGLVQPGGSLRLSCAASGFNIRTQSIHWVRQAPGKGLEWIGDIFPIDGITDYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGSWSWPSGMDYYLDHWGQGTLVTVSS >Light Chain of STRO-002 IgG histidine scanning variant #1(SEQ ID NO: 157)DIQMTQSPSSLSASVGDRVTITCHASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #2 (SEQ ID NO: 158)DIQMTQSPSSLSASVGDRVTITCRHSQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #3 (SEQ ID NO: 159)DIQMTQSPSSLSASVGDRVTITCRAHQDVNTAVAWYQQKPGKAPKWYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #4 (SEQ ID NO: 160)DIQMTQSPSSLSASVGDRVTITCRASHDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #5 (SEQ ID NO: 161)DIQMTQSPSSLSASVGDRVTITCRASQHVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #6 (SEQ ID NO: 162)DIQMTQSPSSLSASVGDRVTITCRASQDHNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #7 (SEQ ID NO: 163)DIQMTQSPSSLSASVGDRVTITCRASQDVHTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #8 (SEQ ID NO: 164)DIQMTQSPSSLSASVGDRVTITCRASQDVNHAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #9 (SEQ ID NO: 165)DIQMTQSPSSLSASVGDRVTITCRASQDVNTHVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #10 (SEQ ID NO: 166)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAHAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #11 (SEQ ID NO: 167)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVHWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #12 (SEQ ID NO: 168)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYHASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #13 (SEQ ID NO: 169)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSHSFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #14 (SEQ ID NO: 170)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSAHFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #15 (SEQ ID NO: 171)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASHLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #16 (SEQ ID NO: 172)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFHYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #17 (SEQ ID NO: 173)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLHSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #18 (SEQ ID NO: 174)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYHGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #19 (SEQ ID NO: 175)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCHQHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #20 (SEQ ID NO: 176)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQHHYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #21 (SEQ ID NO: 177)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #22 (SEQ ID NO: 178)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHHTTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #23 (SEQ ID NO: 179)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYHTPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #24 (SEQ ID NO: 180)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTHPPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #25 (SEQ ID NO: 181)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTHPTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #26 (SEQ ID NO: 182)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPHTFGQGTKVEIK >Light Chain of STRO-002 IgG histidine scanningvariant #27 (SEQ ID NO: 183)DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPHFGQGTKVEIK >Heavy Chain of farletuzumab IgG(SEQ ID NO: 184)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Light Chain of farletuzumab IgG (SEQ ID NO: 185)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Heavy Chain CDR1 of farletuzumab(SEQ ID NO: 186) GFTFSGYGLS >Heavy Chain CDR2 of farletuzumab(SEQ ID NO: 187) MISSGGSYTYYADSVKG >Heavy Chain CDR3 of farletuzumab(SEQ ID NO: 188) ARHGDDPAWFAY >Light Chain CDR1 of farletuzumab(SEQ ID NO: 189) SSISSNNLH >Light Chain CDR2 of farletuzumab(SEQ ID NO: 190) GTSNLAS >Light Chain CDR3 of farletuzumab(SEQ ID NO: 191)QQWSSYPYMYT >Heavy Chain of farletuzumab IgG histidine scanningvariant #1 (SEQ ID NO: 192)EVQLVESGGGVVQPGRSLRLSCSASHFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #2(SEQ ID NO: 193)EVQLVESGGGVVQPGRSLRLSCSASGHTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #3(SEQ ID NO: 194)EVQLVESGGGVVQPGRSLRLSCSASGFHFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #4(SEQ ID NO: 195)EVQLVESGGGVVQPGRSLRLSCSASGFTHSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #5(SEQ ID NO: 196)EVQLVESGGGVVQPGRSLRLSCSASGFTFHGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #6(SEQ ID NO: 197)EVQLVESGGGVVQPGRSLRLSCSASGFTFSHYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #7(SEQ ID NO: 198)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGHGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #8(SEQ ID NO: 199)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYHLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #9(SEQ ID NO: 200)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGHSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #10(SEQ ID NO: 201)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLHWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #11(SEQ ID NO: 202)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAHISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #12(SEQ ID NO: 203)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMHSSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #13(SEQ ID NO: 204)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMIHSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #14(SEQ ID NO: 205)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISHGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #15(SEQ ID NO: 206)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSHGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #16(SEQ ID NO: 207)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGHSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #17(SEQ ID NO: 208)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGHYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #18(SEQ ID NO: 209)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSHTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #19(SEQ ID NO: 210)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYHYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #20(SEQ ID NO: 211)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTHYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #21(SEQ ID NO: 212)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYHADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #22(SEQ ID NO: 213)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYHDSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #23(SEQ ID NO: 214)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYAHSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #24(SEQ ID NO: 215)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADHVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #25(SEQ ID NO: 216)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSHKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #26(SEQ ID NO: 217)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVHGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #27(SEQ ID NO: 218)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKHRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #28(SEQ ID NO: 219)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCHRHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #29(SEQ ID NO: 220)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCAHHGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #30(SEQ ID NO: 221)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARAGDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #31(SEQ ID NO: 222)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHHDDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #32(SEQ ID NO: 223)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGHDPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #33(SEQ ID NO: 224)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDHPAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #34(SEQ ID NO: 225)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDHAWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #35(SEQ ID NO: 226)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPHWFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #36(SEQ ID NO: 227)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAHFAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #37(SEQ ID NO: 228)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWHAYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #38(SEQ ID NO: 229)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFHYWGQGTPVTVSS >Heavy Chain of farletuzumab IgG histidine scanning variant #39(SEQ ID NO: 230)EVQLVESGGGVVQPGRSLRLSCSASGFTFSGYGLSWVRQAPGKGLEWVAMISSGGSYTYYADSVKGRFAISRDNAKNTLFLQMDSLRPEDTGVYFCARHGDDPAWFAHWGQGTPVTVSS >Light Chain of farletuzumab IgG histidine scanning variant #1(SEQ ID NO: 231)DIQLTQSPSSLSASVGDRVTITCSVSHSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #2 (SEQ ID NO: 232)DIQLTQSPSSLSASVGDRVTITCSVSSHISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #3 (SEQ ID NO: 233)DIQLTQSPSSLSASVGDRVTITCSVSSSHSSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #4 (SEQ ID NO: 234)DIQLTQSPSSLSASVGDRVTITCSVSSSIHSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #5 (SEQ ID NO: 235)DIQLTQSPSSLSASVGDRVTITCSVSSSISHNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #6 (SEQ ID NO: 236)DIQLTQSPSSLSASVGDRVTITCSVSSSISSHNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #7 (SEQ ID NO: 237)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNHLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #8 (SEQ ID NO: 238)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNHHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #9 (SEQ ID NO: 239)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLAWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #10 (SEQ ID NO: 240)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYHTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #11 (SEQ ID NO: 241)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGHSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #12 (SEQ ID NO: 242)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTHNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #13 (SEQ ID NO: 243)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSHLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #14 (SEQ ID NO: 244)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNHASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #15 (SEQ ID NO: 245)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLHSGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #16 (SEQ ID NO: 246)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLAHGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #17 (SEQ ID NO: 247)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCHQWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #18 (SEQ ID NO: 248)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQHWSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #19 (SEQ ID NO: 249)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQHSSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #20 (SEQ ID NO: 250)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWHSYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #21 (SEQ ID NO: 251)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSHYPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #22 (SEQ ID NO: 252)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSHPYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #23 (SEQ ID NO: 253)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYHYMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #24 (SEQ ID NO: 254)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPHMYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #25 (SEQ ID NO: 255)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYHYTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #26 (SEQ ID NO: 256)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMHTFGQGTKVEIK >Light Chain of farletuzumab IgG histidine scanningvariant #27 (SEQ ID NO: 257)DIQLTQSPSSLSASVGDRVTITCSVSSSISSNNLHWYQQKPGKAPKPWIYGTSNLASGVPSRFSGSGSGTDYTFTISSLQPEDIATYYCQQWSSYPYMYHFGQGTKVEIK

What is claimed is:
 1. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein: (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or (b) the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0.
 2. The pharmaceutical composition of claim 1, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell.
 3. The pharmaceutical composition of claim 1 or 2, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.
 4. A pharmaceutical composition comprising an effective amount of an antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0; and (b) the composition provides for one or more of: an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC.
 5. The pharmaceutical composition of claim 1 or 4, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain of mirvetuximab with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO: 1; and/or a light chain variable domain of mirvetuximab with one or more amino acids substituted with a histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO: 2; (b) a heavy chain variable domain of STRO-002 with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO: 105; and/or a light chain variable domain of STRO-002 with one or more amino acids substituted with a histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO: 106; and (c) a heavy chain variable domain of farletuzumab with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO: 184; and/or a light chain variable domain of farletuzumab with one or more amino acids substituted with a histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:
 185. 6. The pharmaceutical composition of claim 1 or 4, wherein the first FOLR1-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 3-5 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 6-8 substituted with a histidine; (b) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 107-109 respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 107-109 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 110-112, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 110-112 substituted with a histidine; and (c) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 186-188, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 186-188 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 189-191, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 189-191 substituted with a histidine.
 7. The pharmaceutical composition of any one of claims 1 and 4-6, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 2, wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 105, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 105 selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 106: wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 106 selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; and (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 184, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 184 selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 185, wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 185 selected from the group consisting of 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and
 100. 8. The pharmaceutical composition of claim 1 or 4, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a light chain variable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83, and/or a heavy chain variable domain of SEQ ID NO: 1, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 2 and heavy chain variable domain of SEQ ID NO: 1; (ii) a light chain variable domain of SEQ ID NO: 2 and heavy chain variable domain that is not one of SEQ ID NOs: 14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70, 74, 76-81 and 83; (b) a light chain variable domain of SEQ ID NO: 106, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, or SEQ ID NO: 182, and/or a heavy chain variable domain of SEQ ID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 106 and a heavy chain variable domain of SEQ ID NO: 105; (ii) a light chain variable domain of SEQ ID NO: 106 and a heavy chain variable domain that is not one of SEQ ID NOs: 116, 120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variable domain of SEQ ID NO: 105 and a light chain variable domain that is not one of SEQ ID NOs: 161-164, 168, and 177-182; and (c) a light chain variable domain of SEQ ID NO: 185, SEQ ID NO: 233, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO: 251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, or SEQ ID NO: 257, and/or a heavy chain variable domain of SEQ ID NO: 184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 185 and a heavy chain variable domain of SEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 and a heavy chain variable domain that is not one of SEQ ID NOs: 192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) a heavy chain variable domain of SEQ ID NO: 184 and a light chain variable domain that is not one of SEQ ID NOs: 233, 237-244, 247, 249, 251, and 253-257.
 9. The pharmaceutical composition of any one of claims 1-8, wherein the composition provides for: an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; and/or an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC.
 10. The pharmaceutical composition of any one of claims 1-9, wherein the composition provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC.
 11. The pharmaceutical composition of any one of claims 1-10, wherein the composition: results in a less of a reduction in the level of FOLR1 presented on the surface of the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; or does not result in a detectable reduction in the level of FOLR1 presented on the surface of the target mammalian cell.
 12. The pharmaceutical composition of any one of claims 1-11, wherein the target mammalian cell is a cancer cell.
 13. The pharmaceutical composition of any one of claims 1-12, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cell.
 14. The pharmaceutical composition of any one of claims 1-13, wherein the ABPC is: cross-reactive with a non-human primate FOLR1 and human FOLR1; or cross-reactive with a non-human primate FOLR1, a human FOLR1, and one or both of rat FOLR1 and a mouse FOLR1.
 15. The pharmaceutical composition of any one of claims 1-14, wherein the ABPC comprises a single polypeptide.
 16. The pharmaceutical composition of claim 15, wherein the antigen-binding domain is selected from the group consisting of: a VH domain, a VHH domain, a VNAR domain, and a scFv.
 17. The pharmaceutical composition of any one of claims 1-14, wherein the ABPC comprises two or more polypeptides.
 18. The pharmaceutical composition of claim 17, wherein the ABPC is an antibody.
 19. The pharmaceutical composition of any of claims 1-18, wherein the half-life of the ABPC in vivo is decreased as compared to the half-life of a control ABPC in vivo.
 20. The pharmaceutical composition of any one of claims 1-19, wherein the ABPC further comprises a second antigen-binding domain.
 21. An antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell, wherein: (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or (b) the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0.
 22. The ABPC of claim 21, wherein the ABPC is degraded in the target mammalian cell following internalization of the ABPC by the target mammalian cell.
 23. The ABPC of claim 21 or 22, wherein the ABPC further comprises a conjugated toxin, radioisotope, drug, or small molecule.
 24. An antigen-binding protein construct (ABPC) comprising: a first antigen-binding domain that is capable of specifically binding FOLR1 or an epitope of FOLR1 presented on the surface of a target mammalian cell; and a conjugated toxin, radioisotope, drug, or small molecule, wherein: (a) the dissociation rate of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is faster than the dissociation rate at a pH of about 7.0 to about 8.0; or the dissociation constant (KD) of the first antigen-binding domain at a pH of about 4.0 to about 6.5 is greater than the KD at a pH of about 7.0 to about 8.0; and (b) the composition provides for one or more of: an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC; and an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC.
 25. The ABPC of claim 21 or 24, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain of mirvetuximab with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of mirvetuximab comprises SEQ ID NO: 1; and/or a light chain variable domain of mirvetuximab with one or more amino acids substituted with a histidine, wherein the light chain variable domain of mirvetuximab comprises SEQ ID NO: 2; (b) a heavy chain variable domain of STRO-002 with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of STRO-002 comprises SEQ ID NO: 105; and/or a light chain variable domain of STRO-002 with one or more amino acids substituted with a histidine, wherein the light chain variable domain of STRO-002 comprises SEQ ID NO: 106; and (c) a heavy chain variable domain of farletuzumab with one or more amino acids substituted with a histidine, wherein the heavy chain variable domain of farletuzumab comprises SEQ ID NO: 184; and/or a light chain variable domain of farletuzumab with one or more amino acids substituted with a histidine, wherein the light chain variable domain of farletuzumab comprises SEQ ID NO:
 185. 26. The ABPC of claim 21 or 24, wherein the first FOLR1-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 3-5, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 3-5 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 6-8, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 6-8 substituted with a histidine; (b) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 107-109, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 107-109 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 110-112, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 110-112 substituted with a histidine; and (c) a heavy chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 186-188, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 186-188 substituted with a histidine; and/or a light chain variable domain comprising a CDR1, a CDR2, and a CDR3 of SEQ ID NOs: 189-191, respectively, with collectively a total of one or more amino acid positions in SEQ ID NOs: 189-191 substituted with a histidine.
 27. The ABPC of any one of claims 21 and 24-26, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 1, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 1 selected from the group consisting of: 24, 27, 29, 31, 32, 33, 34, 50, 54, 55, 57, 58, 59, 60, 97, 98, 99, 100, 102, 103, 105, and 107; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 2, wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 2 selected from the group consisting of: 28, 30, 31, 32, 34, 35, 36, 55, 59, 93, 94, 95, 96, 97, 98, and 100; (b) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 105, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 105 selected from the group consisting of: 29, 33, 34, 50, 51, 52, 53, 55, 56, 57, 101, 102, 103, 108, 109, 110, 111, 112, and 113; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 106, wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 106 selected from the group consisting of: 28, 29, 30, 31, 50, 92, 93, 94, 95, and 96; and (c) a heavy chain variable domain that is at least 90% identical to SEQ ID NO: 184, wherein the heavy chain variable domain includes a histidine at one or more positions in SEQ ID NO: 184 selected from the group consisting of: 26, 27, 28, 29, 30, 32, 33, 34, 53, 56, 57, 59, 62, 63, 103, and 105; and/or a light chain variable domain that is at least 90% identical to SEQ ID NO: 185, wherein the light chain variable domain includes a histidine at one or more positions in SEQ ID NO: 185 selected from the group consisting of: 29, 33, 34, 51, 52, 53, 54, 55, 90, 92, 94, 96, 97, 98, 99, and
 100. 28. The ABPC of claim 21 or 24, wherein the first antigen-binding domain comprises one of (a) through (c): (a) a light chain variable domain of SEQ ID NO: 2, SEQ ID NO: 58, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NO: 74, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, or SEQ ID NO: 83, and/or a heavy chain variable domain of SEQ ID NO: 1, SEQ ID NO: 14, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 26, SEQ ID NO: 28, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49, SEQ ID NO: 51, SEQ ID NO: 53, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, or SEQ ID NO: 103, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 2 and heavy chain variable domain of SEQ ID NO: 1; (ii) a light chain variable domain of SEQ ID NO: 2 and heavy chain variable domain that is not one of SEQ ID NOs: 14, 17, 19, 21-24, 26, 28, 30, 31, 33-36, 43-46, 48, 49, 51, 53, and 85-103; (iii) a heavy chain variable domain of SEQ ID NO: 1 and a light chain variable domain that is not one of SEQ ID NOs: 58, 60-62, 64-66, 68, 70, 74, 76-81 and 83; (b) a light chain variable domain of SEQ ID NO: 106, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 168, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, or SEQ ID NO: 182, and/or a heavy chain variable domain of SEQ ID NO: 105, SEQ ID NO: 116, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, or SEQ ID NO: 156, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 106 and a heavy chain variable domain of SEQ ID NO: 105; (ii) a light chain variable domain of SEQ ID NO: 106 and a heavy chain variable domain that is not one of SEQ ID NOs: 116, 120-126,128-130, 144-146, and 151-156; (iii) a heavy chain variable domain of SEQ ID NO: 105 and a light chain variable domain that is not one of SEQ ID NOs: 161-164, 168, and 177-182; and (c) a light chain variable domain of SEQ ID NO: 185, SEQ ID NO: 233, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 247, SEQ ID NO: 249, SEQ ID NO: 251, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, or SEQ ID NO: 257, and/or a heavy chain variable domain of SEQ ID NO: 184, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 205, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 211, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 221, SEQ ID NO: 225, or SEQ ID NO: 227, wherein the first antigen-binding domain does not comprise (i) a light chain variable domain of SEQ ID NO: 185 and a heavy chain variable domain of SEQ ID NO: 184; (ii) a light chain variable domain of SEQ ID NO: 185 and a heavy chain variable domain that is not one of SEQ ID NOs: 192-196, 198-200, 205, 208, 209, 211, 214, 215, 221, 225 and 227; (iii) a heavy chain variable domain of SEQ ID NO: 184 and a light chain variable domain that is not one of SEQ ID NOs: 233, 237-244, 247, 249, 251, and 253-257.
 29. The ABPC of any one of claims 21-28, wherein a composition comprising the ABPC provides for: an increase in toxin liberation in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; and/or an increase in target mammalian cell killing as compared to a composition comprising the same amount of a control ABPC.
 30. The ABPC of any one of claims 21-29, wherein a composition comprising the ABPC provides for an increase in endolysosomal delivery in the target mammalian cell as compared to a composition comprising the same amount of a control ABPC.
 31. The ABPC of any one of claims 21-30, wherein a composition comprising the ABPC: results in a less of a reduction in the level of FOLR1 presented on the surface of the target mammalian cell as compared to a composition comprising the same amount of a control ABPC; or does not result in a detectable reduction in the level of FOLR1 presented on the surface of the target mammalian cell.
 32. The ABPC of any one of claims 21-31, wherein the target mammalian cell is a cancer cell.
 33. The ABPC of any one of claims 21-32, wherein the ABPC is cytotoxic or cytostatic to the target mammalian cell.
 34. The ABPC of any one of claims 21-33, wherein the ABPC is: cross-reactive with a non-human primate FOLR1 and human FOLR1; or cross-reactive with a non-human primate FOLR1, a human FOLR1, and one or both of rat FOLR1 and a mouse FOLR1.
 35. The ABPC of any one of claims 21-34, wherein the ABPC comprises a single polypeptide.
 36. The ABPC of claim 35, wherein the antigen-binding domain is selected from the group consisting of: a VH domain, a VHH domain, a VNAR domain, and a scFv.
 37. The ABPC of any one of claims 21-34, wherein the ABPC comprises two or more polypeptides.
 38. The ABPC of claim 37, wherein the ABPC is an antibody.
 39. The ABPC of any of claims 21-38, wherein the half-life of the ABPC in vivo is decreased as compared to the half-life of a control ABPC in vivo.
 40. The ABPC of any one of claims 21-39, wherein the ABPC further comprises a second antigen-binding domain.
 41. A kit comprising at least one dose of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40.
 42. A method of treating a cancer characterized by having a population of cancer cells that have FOLR1 or an epitope of FOLR1 presented on their surface, the method comprising: administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having a cancer characterized by having the population of cancer cells.
 43. A method of reducing the volume of a tumor in a subject, wherein the tumor is characterized by having a population of cancer cells that have FOLR1 or an epitope of FOLR1 presented on their surface, the method comprising: administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having a cancer characterized by having the population of cancer cells.
 44. A method of inducing cell death in a cancer cell in a subject, wherein the cancer cell has FOLR1 or an epitope of FOLR1 presented on its surface, wherein the method comprises: administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having a cancer characterized by having a population of the cancer cells.
 45. A method of decreasing the risk of developing a metastasis or decreasing the risk of developing an additional metastasis in a subject having a cancer, wherein the cancer is characterized by having a population of cancer cells that have FOLR1 or an epitope of FOLR1 presented on their surface the method comprising: administering a therapeutically effective amount of the pharmaceutical composition of any one of claims 1-20 or the ABPC of any one of claims 21-40 to a subject identified as having a cancer characterized by having the population of cancer cells. 